Parkinson's Disease and Cancer: Mechanistic Insights and Therapeutic Opportunities From Cancer Neuroscience

Abstract

There is a complex pathological association between neurodegenerative diseases and cancer. The epidemiological negative correlation between Parkinson's disease (PD) and brain tumor is particularly noteworthy. PD is characterized by the loss of dopaminergic neurons and the formation of Lewy bodies, while glioma, the representative of brain tumors, originates from the malignant transformation of glial cells. The molecular interaction network between these two diseases is elusive, limiting the development of cross-disease treatment strategies. This review systematically summarizes the associations between PD and glioma in genetic predispositions, epigenetic modifications, alterations in subcellular compartments, and cellular mechanisms concerning neurons, glial cells, and stem cells. Additional links arise from circadian rhythm regulation, oxidative stress, and gut microbiota, underscoring the importance of systemic pathways that connect neurodegeneration and tumorigenesis. Within this context, cancer neuroscience emerges as a critical framework, demonstrating how neuronal activity drives cancer progression by shaping the tumor microenvironment. Therapeutic opportunities build upon these mechanistic insights, including engineering neuron types to suppress cancer growth, modulating synaptic genes, inducing neuronal cell death cascades, and controlling inflammation to disrupt tumor-nerve crosstalk. Emerging neuroscience-inspired technologies may drastically expand the treatment landscape. This review tries to unveil a potential theoretical paradigm for developing precise therapies with both neuroprotection and antitumor effects.

Keywords

cancer / cancer neuroscience / gliomas / neurodegenerative diseases / Parkinson's disease

References

[1] A. Finch, G. Solomou, V. Wykes, U. Pohl, C. Bardella, and C. Watts, “Advances in Research of Adult Gliomas,” International Journal of Molecular Sciences 22, no. 2 (2021): 924.

[2] A. Samii, J. G. Nutt, and B. R. Ransom, “Parkinson's Disease,” Lancet 363, no. 9423 (2004): 1783–1793.

[3] K. Biserova, A. Jakovlevs, R. Uljanovs, and I. Strumfa, “Cancer Stem Cells: Significance in Origin, Pathogenesis and Treatment of Glioblastoma,” Cells 10, no. 3 (2021): 621.

[4] P. Mencke, Z. Hanss, I. Boussaad, P. E. Sugier, A. Elbaz, and R. Krüger, “Bidirectional Relation Between Parkinson's Disease and Glioblastoma Multiforme,” Frontiers in Neurology 11 (2020): 898.

[5] Z. Li, Z. Zheng, J. Ruan, Z. Li, and C. M. Tzeng, “Chronic Inflammation Links Cancer and Parkinson's Disease,” Frontiers in Aging Neuroscience 8 (2016): 126.

[6] S. Smajić, C. A. Prada-Medina, Z. Landoulsi, et al., “Single-Cell Sequencing of Human Midbrain Reveals Glial Activation and a Parkinson-Specific Neuronal State,” Brain 145, no. 3 (2022): 964–978.

[7] A. Kouli, L. R. B. Spindler, T. D. Fryer, et al., “Neuroinflammation Is Linked to Dementia Risk in Parkinson's Disease,” Brain 147, no. 3 (2024): 923–935.

[8] C. Pan and F. Winkler, “Insights and Opportunities at the Crossroads of Cancer and Neuroscience,” Nature Cell Biology 24, no. 10 (2022): 1454–1460.

[9] P. E. Sugier, E. A. Lucotte, C. Domenighetti, et al., “Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers,” Movement Disorders 38, no. 4 (2023): 604–615.

[10] D. Singh, “Astrocytic and Microglial Cells as the Modulators of Neuroinflammation in Alzheimer's Disease,” Journal of Neuroinflammation 19, no. 1 (2022): 206.

[11] H. S. Kwon and S. H. Koh, “Neuroinflammation in Neurodegenerative Disorders: The Roles of Microglia and Astrocytes,” Translational Neurodegeneration 9, no. 1 (2020): 42.

[12] D. Li, K. Yang, J. Li, et al., “Single-Cell Sequencing Reveals Glial Cell Involvement in Development of Neuropathic Pain via Myelin Sheath Lesion Formation in the Spinal Cord,” Journal of Neuroinflammation 21, no. 1 (2024): 213.

[13] C. Taveggia and M. L. Feltri, “Beyond Wrapping: Canonical and Noncanonical Functions of Schwann Cells,” Annual Review of Neuroscience 45 (2022): 561–580.

[14] B. Zhu, D. Yin, H. Zhao, and L. Zhang, “The Immunology of Parkinson's Disease,” Seminars in Immunopathology 44, no. 5 (2022): 659–672.

[15] L. Xu, D. Lin, D. Yin, and H. P. Koeffler, “An Emerging Role of PARK2 in Cancer,” Journal of Molecular Medicine 92, no. 1 (2014): 31–42.

[16] R. Saunders-Pullman, M. J. Barrett, K. M. Stanley, et al., “LRRK2 G2019S Mutations Are Associated With an Increased Cancer Risk in Parkinson Disease,” Movement Disorders 25, no. 15 (2010): 2536–2541.

[17] H. Eo, S. Kim, U. J. Jung, and S. R. Kim, “Alpha-Synuclein and Microglia in Parkinson's Disease: From Pathogenesis to Therapeutic Prospects,” Journal of Clinical Medicine 13, no. 23 (2024): 7243.

[18] D. Hambardzumyan and G. Bergers, “Glioblastoma: Defining Tumor Niches,” Trends in Cancer 1, no. 4 (2015): 252–265.

[19] S. Veeriah, B. S. Taylor, S. Meng, et al., “Somatic Mutations of the Parkinson's Disease-Associated Gene PARK2 in Glioblastoma and Other Human Malignancies,” Nature Genetics 42, no. 1 (2010): 77–82.

[20] M. R. Cookson, “LRRK2 Pathways Leading to Neurodegeneration,” Current Neurology and Neuroscience Reports 15, no. 7 (2015): 42.

[21] S. D. Nielsen, N. M. Pearson, and K. Seidler, “The Link Between the Gut Microbiota and Parkinson's Disease: A Systematic Mechanism Review With Focus on α-Synuclein Transport,” Brain Research 1769 (2021): 147609.

[22] S. Zhao, H. Chi, Q. Yang, et al., “Identification and Validation of Neurotrophic Factor-Related Gene Signatures in Glioblastoma and Parkinson's Disease,” Frontiers in immunology 14 (2023): 1090040.

[23] H. Zhu, H. Wang, Q. Huang, et al., “Transcriptional Repression of p53 by PAX3 Contributes to Gliomagenesis and Differentiation of Glioma Stem Cells,” Frontiers in Molecular Neuroscience 11 (2018): 187.

[24] X. Sun, O. Klingbeil, B. Lu, et al., “BRD8 Maintains Glioblastoma by Epigenetic Reprogramming of the p53 Network,” Nature 613, no. 7942 (2023): 195–202.

[25] A. Szybińska and L. Leśniakx, “P53 Dysfunction in Neurodegenerative Disease—The Cause or Effect of Pathological Changes?,” Aging and Disease 8, no. 4 (2017): 506–518.

[26] E. Duplan, C. Giordano, F. Checler, and C. Alves da Costa, “Direct Alpha-Synuclein Promoter Transactivation by the Tumor Suppressor P53,” Molecular Neurodegeneration 11 (2016): 13.

[27] H. Kim, J. Y. Shin, A. Jo, et al., “Parkin Interacting Substrate Phosphorylation by c-Abl Drives Dopaminergic Neurodegeneration,” Brain 144, no. 12 (2021): 3674–3691.

[28] P. Wang, L. Zhao, S. Gong, et al., “HIF1α/HIF2α–Sox2/Klf4 Promotes the Malignant Progression of Glioblastoma via the EGFR–PI3K/AKT Signalling Pathway With Positive Feedback Under Hypoxia,” Cell Death & Disease 12, no. 4 (2021): 312.

[29] H. Zheng, H. Ying, H. Yan, et al., “p53 and Pten Control Neural and Glioma Stem/Progenitor Cell Renewal and Differentiation,” Nature 455, no. 7216 (2008): 1129–1133.

[30] S. Timmons, M. F. Coakley, A. M. Moloney, and C. O’ Neill, “Akt Signal Transduction Dysfunction in Parkinson's Disease,” Neuroscience Letters 467, no. 1 (2009): 30–35.

[31] Y. X. Li, Z. W. Yu, T. Jiang, et al., “SNCA, a Novel Biomarker for Group 4 Medulloblastomas, Can Inhibit Tumor Invasion and Induce Apoptosis,” Cancer science 109, no. 4 (2018): 1263–1275.

[32] T. L. Scott, C. A. Wicker, R. Suganya, et al., “Polyubiquitination of Apurinic/Apyrimidinic Endonuclease 1 by Parkin,” Molecular Carcinogenesis 56, no. 2 (2017): 325–336.

[33] R. Gargini, B. Segura-Collar, and P. Sánchez-Gómez, “Novel Functions of the Neurodegenerative-Related Gene Tau in Cancer,” Frontiers in Aging Neuroscience 11 (2019): 231.

[34] Y. Shi, K. Yamada, S. A. Liddelow, et al., “ApoE4 Markedly Exacerbates Tau-Mediated Neurodegeneration in a Mouse Model of Tauopathy,” Nature 549, no. 7673 (2017): 523–527.

[35] Q. Ye, P. Srivastava, N. Al-Kuwari, and X. Chen, “Oncogenic BRAF(V600E) Induces Microglial Proliferation Through Extracellular Signal-Regulated Kinase and Neuronal Death Through c-Jun N-Terminal Kinase,” Neural Regeneration Research 18, no. 7 (2023): 1613–1622.

[36] E. Leem, H. J. Kim, M. Choi, et al., “Upregulation of Neuronal Astrocyte Elevated Gene-1 Protects Nigral Dopaminergic Neurons In Vivo,” Cell Death & Disease 9, no. 5 (2018): 449.

[37] L. Emdad, D. Sarkar, Z. Z. Su, et al., “Astrocyte Elevated Gene-1: Recent Insights Into a Novel Gene Involved in Tumor Progression, Metastasis and Neurodegeneration,” Pharmacology & Therapeutics 114, no. 2 (2007): 155–170.

[38] G. Hu, Y. Wei, and Y. Kang, “The Multifaceted Role of MTDH/AEG-1 in Cancer Progression,” Clinical Cancer Research 15, no. 18 (2009): 5615–5620.

[39] J. T. Low, M. C. Brown, Z. J. Reitman, et al., “Understanding and Therapeutically Exploiting cGAS/Sting Signaling in Glioblastoma,” Journal of Clinical Investigation 134, no. 2 (2024): e163452.

[40] A. M. Pickrell and R. J. Youle, “The Roles of PINK1, Parkin, and Mitochondrial Fidelity in Parkinson's Disease,” Neuron 85, no. 2 (2015): 257–273.

[41] M. Hao, Y. Liang, R. Guo, et al., “Advances of Glioma Biomarkers,” Sheng wu gong cheng xue bao = Chinese Journal of Biotechnology 39, no. 4 (2023): 1445–1461.

[42] K. Kanwore, X. Guo, A. A. Abdulrahman, P. A. Kambey, I. Nadeem, and D. Gao, “SOX1 Is a Backup Gene for Brain Neurons and Glioma Stem Cell Protection and Proliferation,” Molecular Neurobiology 58, no. 6 (2021): 2634–2642.

[43] A. Zimran, S. Revel-Vilk, M. Becker-Cohen, M. Istaiti, and A. Rolfs, “Venglustat in GBA1-related Parkinson's Disease,” Lancet Neurology 23, no. 2 (2024): 137.

[44] N. H. Stillman, J. A. Joseph, J. Ahmed, et al., “Protein Mimetic 2D Fast Rescues Alpha Synuclein Aggregation Mediated Early and Post Disease Parkinson's Phenotypes,” Nature Communications 15, no. 1 (2024): 3658.

[45] A. Zbinden, M. Pérez-Berlanga, P. De Rossi, and M. Polymenidou, “Phase Separation and Neurodegenerative Diseases: A Disturbance in the Force,” Developmental Cell 55, no. 1 (2020): 45–68.

[46] L. Simone, F. Pisani, M. G. Mola, et al., “AQP4 Aggregation State Is a Determinant for Glioma Cell Fate,” Cancer Research 79, no. 9 (2019): 2182–2194.

[47] Y. Rasmi, A. Shokati, A. Hassan, et al., “The Role of Dna Methylation in Progression of Neurological Disorders and Neurodegenerative Diseases as Well as the Prospect of Using DNA Methylation Inhibitors as Therapeutic Agents for Such Disorders,” IBRO Neuroscience Reports 14 (2023): 28–37.

[48] R. Chaligne, F. Gaiti, D. Silverbush, et al., “Epigenetic Encoding, Heritability and Plasticity of Glioma Transcriptional Cell States,” Nature Genetics 53, no. 10 (2021): 1469–1479.

[49] L. Chen, Q. Qi, X. Jiang, et al., “Phosphocreatine Promotes Epigenetic Reprogramming to Facilitate Glioblastoma Growth Through Stabilizing BRD2,” Cancer Discovery 14, no. 8 (2024): 1547–1565.

[50] H. J. Jang, N. M. Shah, J. H. Maeng, et al., “Epigenetic Therapy Potentiates Transposable Element Transcription to Create Tumor-Enriched Antigens in Glioblastoma Cells,” Nature Genetics 56, no. 9 (2024): 1903–1913.

[51] Y. Liu, H. Ali, F. Khan, L. Pang, and P. Chen, “Epigenetic Regulation of Tumor-Immune Symbiosis in Glioma,” Trends in Molecular Medicine 30, no. 5 (2024): 429–442.

[52] S. I. Sherwani and H. A. Khan, “Role of 5-Hydroxymethylcytosine in Neurodegeneration,” Gene 570, no. 1 (2015): 17–24.

[53] Q. Xie, T. P. Wu, R. C. Gimple, et al., “N-Methyladenine DNA Modification in Glioblastoma,” Cell 175, no. 5 (2018): 1228–1243 e20.

[54] T. T. Wu, T. Liu, X. Li, et al., “TET2-Mediated Cdkn2A DNA Hydroxymethylation in Midbrain Dopaminergic Neuron Injury of Parkinson's Disease,” Human Molecular Genetics 29, no. 8 (2020): 1239–1252.

[55] L. Zang, S. M. Kondengaden, F. Che, L. Wang, and X. Heng, “Potential Epigenetic-Based Therapeutic Targets for Glioma,” Frontiers in Molecular Neuroscience 11 (2018): 408.

[56] D. Zhang, J. Zhang, Y. Wang, et al., “Targeting Epigenetic Modifications in Parkinson's Disease Therapy,” Medicinal Research Reviews 43, no. 5 (2023): 1748–1777.

[57] A. Jowaed, I. Schmitt, O. Kaut, and U. Wüllner, “Methylation Regulates Alpha-Synuclein Expression and Is Decreased in Parkinson's Disease Patients' Brains,” Journal of Neuroscience 30, no. 18 (2010): 6355–6359.

[58] B. Kantor, L. Tagliafierro, J. Gu, et al., “Downregulation of SNCA Expression by Targeted Editing of DNA Methylation: A Potential Strategy for Precision Therapy in PD,” Molecular Therapy 26, no. 11 (2018): 2638–2649.

[59] G. Kaur, S. S. S. Rathod, M. M. Ghoneim, et al., “DNA Methylation: A Promising Approach in Management of Alzheimer's Disease and Other Neurodegenerative Disorders,” Biology 11, no. 1 (2022): 90.

[60] I. A. Qureshi and M. F. Mehler, “Epigenetic Mechanisms Governing the Process of Neurodegeneration,” Molecular Aspects of Medicine 34, no. 4 (2013): 875–882.

[61] S. Long, G. Huang, M. Ouyang, et al., “Epigenetically Modified AP-2α by DNA Methyltransferase Facilitates Glioma Immune Evasion by Upregulating PD-L1 Expression,” Cell Death & Disease 14, no. 6 (2023): 365.

[62] Y. Yamamoto, K. Higashimoto, Y. Ohkawa, et al., “Possible Regulation of Ganglioside GD3 Synthase Gene Expression With DNA Methylation in Human Glioma Cells,” Glycoconjugate Journal 40, no. 3 (2023): 323–332.

[63] X. Chen, X. Huang, C. Wang, et al., “DNA Methylation-Regulated YTHDF2 Correlates With Cell Migration and Immune Cell Infiltration in Glioma,” Aging (Albany NY) 14, no. 19 (2022): 7774–7793.

[64] Z. Yang, Y. He, Y. Wang, et al., “Genome-Wide Analysis for the Regulation of Gene Alternative Splicing by DNA Methylation Level in Glioma and Its Prognostic Implications,” Frontiers in Genetics 13 (2022): 799913.

[65] L. P. Sarin and S. A. Leidel, “Modify or Die? RNA Modification Defects in Metazoans,” RNA Biology 11, no. 12 (2014): 1555–1567.

[66] C. Labbé, O. Lorenzo-Betancor, and O. A. Ross, “Epigenetic Regulation in Parkinson's Disease,” Acta Neuropathologica 132, no. 4 (2016): 515–530.

[67] J. Lv, L. Xing, X. Zhong, K. Li, M. Liu, and K. Du, “Role of N6-methyladenosine Modification in Central Nervous System Diseases and Related Therapeutic Agents,” Biomedicine & Pharmacotherapy 162 (2023): 114583.

[68] Z. Yu, L. Huang, Y. Xia, et al., “Analysis of m6A Modification Regulators in the Substantia Nigra and Striatum of MPTP-Induced Parkinson's Disease Mice,” Neuroscience Letters 791 (2022): 136907.

[69] X. Chen, C. Yu, M. Guo, et al., “Down-Regulation of m6A mRNA Methylation Is Involved in Dopaminergic Neuronal Death,” ACS Chemical Neuroscience 10, no. 5 (2019): 2355–2363.

[70] D. Dixit, B. C. Prager, R. C. Gimple, et al., “The RNA m6A Reader YTHDF2 Maintains Oncogene Expression and Is a Targetable Dependency in Glioblastoma Stem Cells,” Cancer Discovery 11, no. 2 (2021): 480–499.

[71] B. Li, R. Zhao, W. Qiu, et al., “The N(6)-methyladenosine-mediated lncRNA WEE2-AS1 Promotes Glioblastoma Progression by Stabilizing RPN2,” Theranostics 12, no. 14 (2022): 6363–6379.

[72] X. Ji, Z. Liu, J. Gao, et al., “N(6)-Methyladenosine-modified lncRNA LINREP promotes Glioblastoma Progression by Recruiting the PTBP1/HuR Complex,” Cell Death & Differentiation 30, no. 1 (2023): 54–68.

[73] V. Tassinari, V. Cesarini, S. Tomaselli, et al., “ADAR1 Is a New Target of METTL3 and Plays a Pro-Oncogenic Role in Glioblastoma by an Editing-Independent Mechanism,” Genome Biology 22, no. 1 (2021): 51.

[74] J. Landgrave-Gómez, O. Mercado-Gómez, and R. Guevara-Guzmán, “Epigenetic Mechanisms in Neurological and Neurodegenerative Diseases,” Frontiers in Cellular Neuroscience 9 (2015): 58.

[75] M. D. Plazas-Mayorca and K. E. Vrana, “Proteomic Investigation of Epigenetics in Neuropsychiatric Disorders: A Missing Link Between Genetics and Behavior?,” Journal of Proteome Research 10, no. 1 (2011): 58–65.

[76] S. Guhathakurta, J. Kim, L. Adams, et al., “Targeted Attenuation of Elevated Histone Marks Atsncaalleviates α-Synuclein in Parkinson's Disease,” EMBO Molecular Medicine 13, no. 2 (2021): e12188.

[77] H. Song, J. Chen, J. Huang, et al., “Epigenetic Modification in Parkinson's Disease,” Frontiers in Cell and Developmental Biology 11 (2023): 1123621.

[78] J. Do, C. McKinney, P. Sharma, and E. Sidransky, “Glucocerebrosidase and Its Relevance to Parkinson Disease,” Molecular Neurodegeneration 14, no. 1 (2019): 36.

[79] T. F. Outeiro, E. Kontopoulos, S. M. Altmann, et al., “Sirtuin 2 Inhibitors Rescue α-Synuclein-Mediated Toxicity in Models of Parkinson's Disease,” Science 317, no. 5837 (2007): 516–519.

[80] M. Mazzocchi, L. M. Collins, A. M. Sullivan, and G. W. O'Keeffe, “The Class II Histone Deacetylases as Therapeutic Targets for Parkinson's Disease,” Neuronal Signaling 4, no. 2 (2020): NS20200001.

[81] W. Yang, Y. Xia, D. Hawke, et al., “PKM2 Phosphorylates Histone H3 and Promotes Gene Transcription and Tumorigenesis,” Cell 150, no. 4 (2012): 685–696.

[82] X. Wei, B. Xiao, L. Wang, L. Zang, and F. Che, “Potential New Targets and Drugs Related to Histone Modifications in Glioma Treatment,” Bioorganic Chemistry 112 (2021): 104942.

[83] I. F. Harrison and D. T. Dexter, “Epigenetic Targeting of Histone Deacetylase: Therapeutic Potential in Parkinson's Disease?,” Pharmacology & Therapeutics 140, no. 1 (2013): 34–52.

[84] E. Kunadis, E. Lakiotaki, P. Korkolopoulou, and C. Piperi, “Targeting Post-Translational Histone Modifying Enzymes in Glioblastoma,” Pharmacology & Therapeutics 220 (2021): 107721.

[85] R. Pacaud, M. Cheray, A. Nadaradjane, F. M. Vallette, and P. F. Cartron, “Histone H3 Phosphorylation in GBM: A New Rational to Guide the Use of Kinase Inhibitors in Anti-GBM Therapy,” Theranostics 5, no. 1 (2015): 12–22.

[86] M. A. Varela, T. C. Roberts, and M. J. A. Wood, “Epigenetics and ncRNAs in Brain Function and Disease: Mechanisms and Prospects for Therapy,” Neurotherapeutics 10, no. 4 (2013): 621–631.

[87] H. Yamada, “Regulatory Non-Coding RNAs in Nervous System Development and Disease,” Frontiers in Bioscience 24, no. 7 (2019): 1203–1240.

[88] S. H. Kim, K. H. Lim, S. Yang, and J. Y. Joo, “Long Non-Coding RNAs in Brain Tumors: Roles and Potential as Therapeutic Targets,” Journal of Hematology & Oncology 14, no. 1 (2021): 77.

[89] Z. Qin, P. Y. Wang, D. F. Su, and X. Liu, “miRNA-124 in Immune System and Immune Disorders,” Frontiers in immunology 7 (2016): 406.

[90] Z. Shi, Q. Chen, C. Li, et al., “MiR-124 Governs Glioma Growth and Angiogenesis and Enhances Chemosensitivity by Targeting R-Ras and N-Ras,” Neuro-Oncology 16, no. 10 (2014): 1341–1353.

[91] E. Angelopoulou, Y. N. Paudel, and C. Piperi, “miR-124 and Parkinson's Disease: A Biomarker With Therapeutic Potential,” Pharmacological Research 150 (2019): 104515.

[92] J. Godlewski, J. Lenart, and E. Salinska, “MicroRNA in Brain Pathology: Neurodegeneration the Other Side of the Brain Cancer,” Non-Coding RNA 5, no. 1 (2019): 20.

[93] L. Thomas, T. Florio, and C. Perez-Castro, “Extracellular Vesicles Loaded miRNAs as Potential Modulators Shared Between Glioblastoma, and Parkinson's and Alzheimer's Diseases,” Frontiers in Cellular Neuroscience 14 (2020): 590034.

[94] S. Yang, K. H. Lim, S. H. Kim, and J. Y. Joo, “Molecular Landscape of Long Noncoding RNAs in Brain Disorders,” Molecular Psychiatry 26, no. 4 (2021): 1060–1074.

[95] Y. Chen, Z. Li, X. Chen, and S. Zhang, “Long Non-Coding RNAs: From Disease Code to Drug Role,” Acta Pharmaceutica Sinica B 11, no. 2 (2021): 340–354.

[96] T. F. J. Kraus, M. Haider, J. Spanner, M. Steinmaurer, V. Dietinger, and H. A. Kretzschmar, “Altered Long Noncoding RNA Expression Precedes the Course of Parkinson's Disease—A Preliminary Report,” Molecular Neurobiology 54, no. 4 (2017): 2869–2877.

[97] L. Zhong, P. Liu, J. Fan, and Y. Luo, “Long Non-Coding RNA H19: Physiological Functions and Involvements in Central Nervous System Disorders,” Neurochemistry International 148 (2021): 105072.

[98] L. Statello, C. J. Guo, L. L. Chen, and M. Huarte, “Gene Regulation by Long Non-Coding RNAs and Its Biological Functions,” Nature Reviews Molecular Cell Biology 22, no. 2 (2021): 96–118.

[99] K. Li and Z. Wang, “lncRNA NEAT1: Key Player in Neurodegenerative Diseases,” Ageing Research Reviews 86 (2023): 101878.

[100] K. Zhou, C. Zhang, H. Yao, et al., “Knockdown of Long Non-Coding RNA NEAT1 Inhibits Glioma Cell Migration and Invasion via Modulation of SOX2 Targeted by miR-132,” Molecular cancer 17, no. 1 (2018): 105.

[101] S. S. Titze-de-Almeida and R. Titze-de-Almeida, “Progress in circRNA-Targeted Therapy in Experimental Parkinson's Disease,” Pharmaceutics 15, no. 8 (2023): 2035.

[102] M. Hanan, A. Simchovitz, N. Yayon, et al., “A Parkinson's Disease CircRNAs Resource Reveals a Link Between circSLC8A1 and Oxidative Stress,” EMBO Molecular Medicine 12, no. 9 (2020): e11942.

[103] J. Zhu, X. Liu, Z. Luan, et al., “Circular RNA circSLC8A1 Inhibits the Proliferation and Invasion of Glioma Cells Through Targeting the miR-214-5p/CDC27 Axis,” Metabolic Brain Disease 37, no. 4 (2022): 1015–1023.

[104] Z. Pan, R. Zhao, B. Li, et al., “EWSR1-induced circNEIL3 Promotes Glioma Progression and Exosome-Mediated Macrophage Immunosuppressive Polarization via Stabilizing IGF2BP3,” Molecular Cancer 21, no. 1 (2022): 16.

[105] Y. Jiang, J. Zhao, R. Li, et al., “CircLRFN5 Inhibits the Progression of Glioblastoma via PRRX2/GCH1 Mediated Ferroptosis,” Journal of Experimental & Clinical Cancer Research 41, no. 1 (2022): 307.

[106] J. Lou, Y. Hao, K. Lin, et al., “Circular RNA CDR1as Disrupts the p53/MDM2 Complex to Inhibit Gliomagenesis,” Molecular Cancer 19, no. 1 (2020): 138.

[107] Y. Wei, C. Lu, P. Zhou, et al., “EIF4A3-induced Circular RNA ASAP1 Promotes Tumorigenesis and Temozolomide Resistance of Glioblastoma via NRAS/MEK1/ERK1-2 Signaling,” Neuro-Oncology 23, no. 4 (2021): 611–624.

[108] J. He, Z. Huang, M. He, et al., “Circular RNA MAPK4 (circ-MAPK4) Inhibits Cell Apoptosis via MAPK Signaling Pathway by Sponging miR-125a-3p in Gliomas,” Molecular Cancer 19, no. 1 (2020): 17.

[109] R. Wang, S. Zhang, X. Chen, et al., “Correction To: EIF4A3-induced Circular RNA MMP9 (circMMP9) Acts as a Sponge of miR-124 and Promotes Glioblastoma Multiforme Cell Tumorigenesis,” Molecular Cancer 19, no. 1 (2020): 153.

[110] F. E. Murillo-González, R. García-Aguilar, L. Vega, and G. Elizondo, “Regulation of Parkin Expression as the Key Balance Between Neural Survival and Cancer Cell Death,” Biochemical Pharmacology 190 (2021): 114650.

[111] T. Srinivas, C. Mathias, C. Oliveira-Mateos, and S. Guil, “Roles of lncRNAs in brain development and Pathogenesis: Emerging Therapeutic Opportunities,” Molecular Therapy 31, no. 6 (2023): 1550–1561.

[112] S. N. Uppala, K. P. Tryphena, P. Naren, S. Srivastava, S. B. Singh, and D. K. Khatri, “Involvement of MiRNA on Epigenetics Landscape of Parkinson's Disease: From Pathogenesis to Therapeutics,” Mechanisms of Ageing and Development 213 (2023): 111826.

[113] G. Xu, C. Ma, and Y. Yang, “Intervention Strategies for Parkinson's Disease: The Role of Exercise and Mitochondria,” Frontiers in Aging Neuroscience 17 (2025): 1519672.

[114] L. Chen, H. Zhang, C. Shang, and Y. Hong, “The Role and Applied Value of Mitochondria in Glioma-Related Research,” CNS Neuroscience & Therapeutics 30, no. 12 (2024): e70121.

[115] C. Hetz and B. Mollereau, “Disturbance of Endoplasmic Reticulum Proteostasis in Neurodegenerative Diseases,” Nature Reviews Neuroscience 15, no. 4 (2014): 233–249.

[116] G. Auf, A. Jabouille, S. Guérit, et al., “Inositol-Requiring Enzyme 1α Is a Key Regulator of Angiogenesis and Invasion in Malignant Glioma,” Proceedings of the National Academy of Sciences 107, no. 35 (2010): 15553–15558.

[117] K. Su, D. Bourdette, and M. Forte, “Genetic Inactivation of Mitochondria-Targeted Redox Enzyme p66ShcA Preserves Neuronal Viability and Mitochondrial Integrity in Response to Oxidative Challenges,” Frontiers in Physiology 3 (2012): 285.

[118] S. H. Yang, W. Li, N. Sumien, M. Forster, J. W. Simpkins, and R. Liu, “Alternative Mitochondrial Electron Transfer for the Treatment of Neurodegenerative Diseases and Cancers: Methylene Blue Connects the Dots,” Progress in Neurobiology 157 (2017): 273–291.

[119] O. Harding, E. Holzer, J. F. Riley, S. Martens, and E. L. F. Holzbaur, “Damaged Mitochondria Recruit the Effector NEMO to Activate NF-κB Signaling,” Molecular Cell 83, no. 17 (2023): 3188–3204.e7.

[120] K. Y. Ma, M. R. Fokkens, F. Reggiori, M. Mari, and D. S. Verbeek, “Parkinson's Disease-Associated VPS35 Mutant Reduces Mitochondrial Membrane Potential and Impairs PINK1/Parkin-Mediated Mitophagy,” Translational Neurodegeneration 10, no. 1 (2021): 19.

[121] I. Irrcher, H. Aleyasin, E. L. Seifert, et al., “Loss of the Parkinson's Disease-Linked Gene DJ-1 Perturbs Mitochondrial Dynamics,” Human Molecular Genetics 19, no. 19 (2010): 3734–3746.

[122] H. Matsui, J. Ito, N. Matsui, T. Uechi, O. Onodera, and A. Kakita, “Cytosolic dsDNA of Mitochondrial Origin Induces Cytotoxicity and Neurodegeneration in Cellular and Zebrafish Models of Parkinson's Disease,” Nature Communications 12, no. 1 (2021): 3101.

[123] T. Nie, K. Tao, L. Zhu, et al., “Chaperone-Mediated Autophagy Controls the Turnover of E3 Ubiquitin Ligase MARCHF5 and Regulates Mitochondrial Dynamics,” Autophagy 17, no. 10 (2021): 2923–2938.

[124] S. Franco-Iborra, M. Vila, and C. Perier, “The Parkinson Disease Mitochondrial Hypothesis: Where Are We At?,” Neuroscientist 22, no. 3 (2016): 266–277.

[125] J. S. Choi, C. Park, and J. W. Jeong, “AMP-Activated Protein Kinase Is Activated in Parkinson's Disease Models Mediated by 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine,” Biochemical and Biophysical Research Communications 391, no. 1 (2010): 147–151.

[126] J. Y. Heo, A. H. Park, M. J. Lee, et al., “Crif1 Deficiency in Dopamine Neurons Triggers Early-Onset Parkinsonism,” Molecular Psychiatry 28, no. 10 (2023): 4474–4484.

[127] D. C. Watson, D. Bayik, S. Storevik, et al., “GAP43-Dependent Mitochondria Transfer From Astrocytes Enhances Glioblastoma Tumorigenicity,” Nature Cancer 4, no. 5 (2023): 648–664.

[128] Y. Fu, D. Wang, H. Wang, et al., “TSPO Deficiency Induces Mitochondrial Dysfunction, Leading to Hypoxia, Angiogenesis, and a Growth-Promoting Metabolic Shift Toward Glycolysis in Glioblastoma,” Neuro-Oncology 22, no. 2 (2020): 240–252.

[129] C. Duman, K. Yaqubi, A. Hoffmann, et al., “Acyl-CoA-Binding Protein Drives Glioblastoma Tumorigenesis by Sustaining Fatty Acid Oxidation,” Cell Metabolism 30, no. 2 (2019): 274–289.e5.

[130] F. Puca, F. Yu, C. Bartolacci, et al., “Medium-Chain Acyl-CoA Dehydrogenase Protects Mitochondria From Lipid Peroxidation in Glioblastoma,” Cancer Discovery 11, no. 11 (2021): 2904–2923.

[131] J. Jung, Y. Zhang, O. Celiku, et al., “Mitochondrial NIX Promotes Tumor Survival in the Hypoxic Niche of Glioblastoma,” Cancer Research 79, no. 20 (2019): 5218–5232.

[132] C. H. Chien, J. Y. Chuang, S. T. Yang, et al., “Enrichment of Superoxide Dismutase 2 in Glioblastoma Confers to Acquisition of Temozolomide Resistance That Is Associated With Tumor-Initiating Cell Subsets,” Journal of Biomedical Science 26, no. 1 (2019): 77.

[133] E. Poteet, G. R. Choudhury, A. Winters, et al., “Reversing the Warburg Effect as a Treatment for Glioblastoma,” Journal of Biological Chemistry 288, no. 13 (2013): 9153–9164.

[134] S. A. Oakes and F. R. Papa, “The Role of Endoplasmic Reticulum Stress in Human Pathology,” Annual Review of Pathology: Mechanisms of Disease 10 (2015): 173–194.

[135] B. D. Roussel, A. J. Kruppa, E. Miranda, D. C. Crowther, D. A. Lomas, and S. J. Marciniak, “Endoplasmic Reticulum Dysfunction in Neurological Disease,” Lancet Neurology 12, no. 1 (2013): 105–118.

[136] I. Stojkovska, W. Y. Wani, F. Zunke, et al., “Rescue of α-Synuclein Aggregation in Parkinson's Patient Neurons by Synergistic Enhancement of ER Proteostasis and Protein Trafficking,” Neuron 110, no. 3 (2022): 436–451 e11.

[137] H. Zhang, B. Ma, N. Li, et al., “SNHG1, a KLF4-Upregulated Gene, Promotes Glioma Cell Survival and Tumorigenesis Under Endoplasmic Reticulum Stress by Upregulating BIRC3 Expression,” Journal of Cellular and Molecular Medicine 27, no. 13 (2023): 1806–1819.

[138] S. Liu, Y. Ba, C. Li, and G. Xu, “Inactivation of CACNA1H Induces Cell Apoptosis by Initiating Endoplasmic Reticulum Stress in Glioma,” Translational Neuroscience 14, no. 1 (2023): 20220285.

[139] Z. Yan, Y. Hu, Y. Zhang, Q. Pu, L. Chu, and J. Liu, “Effects of Endoplasmic Reticulum Stress-Mediated CREB3L1 on Apoptosis of Glioma Cells,” Molecular and Clinical Oncology 16, no. 4 (2022): 83.

[140] X. Chen and J. R. Cubillos-Ruiz, “Endoplasmic Reticulum Stress Signals in the Tumour and Its Microenvironment,” Nature Reviews Cancer 21, no. 2 (2021): 71–88.

[141] J. M. Silva, A. Wong, V. Carelli, and G. A. Cortopassi, “Inhibition of Mitochondrial Function Induces an Integrated Stress Response in Oligodendroglia,” Neurobiology of Disease 34, no. 2 (2009): 357–365.

[142] E. Park, J. Gim, D. K. Kim, C. S. Kim, and H. S. Chun, “Protective Effects of Alpha-Lipoic Acid on Glutamate-Induced Cytotoxicity in C6 Glioma Cells,” Biological and Pharmaceutical Bulletin 42, no. 1 (2019): 94–102.

[143] S. K. Barodia, K. Prabhakaran, S. Karunakaran, V. Mishra, and V. Tapias, “Editorial: Mitochondria and Endoplasmic Reticulum Dysfunction in Parkinson's Disease,” Frontiers in Neuroscience 13 (2019): 1171.

[144] M. Rodríguez-Arribas, S. M. S. Yakhine-Diop, J. M. B. S. Pedro, et al., “Mitochondria-Associated Membranes (MAMs): Overview and Its Role in Parkinson's Disease,” Molecular Neurobiology 54, no. 8 (2017): 6287–6303.

[145] C. A. Perez-Leanos, H. E. Romero-Campos, G. Dupont, and V. Gonzalez-Velez, “ Reduction of ER-Mitochondria Distance: A Key Feature in Alzheimer's and Parkinson's Disease, and During Cancer Treatment.” Annual International Conference of the IEEE Engineering in Medicine and Biology Society (2021). 2021, 4412–4415.

[146] C. Guardia-Laguarta, E. Area-Gomez, C. Rüb, et al., “α-Synuclein Is Localized to Mitochondria-Associated ER Membranes,” Journal of Neuroscience 34, no. 1 (2014): 249–259.

[147] G. Arismendi-Morillo, A. Castellano-Ramírez, and T. N. Seyfried, “Ultrastructural Characterization of the Mitochondria-Associated Membranes Abnormalities in Human Astrocytomas: Functional and Therapeutics Implications,” Ultrastructural Pathology 41, no. 3 (2017): 234–244.

[148] D. Chatterjee and O. Chakrabarti, “Role of Stress Granules in Modulating Senescence and Promoting Cancer Progression: Special Emphasis on Glioma,” International Journal of Cancer 150, no. 4 (2022): 551–561.

[149] B. Wolozin and P. Ivanov, “Stress Granules and Neurodegeneration,” Nature Reviews Neuroscience 20, no. 11 (2019): 649–666.

[150] M. Repici, M. Hassanjani, D. C. Maddison, et al., “The Parkinson's Disease-Linked Protein DJ-1 Associates With Cytoplasmic mRNP Granules During Stress and Neurodegeneration,” Molecular Neurobiology 56, no. 1 (2019): 61–77.

[151] S. Paul, W. Dansithong, K. P. Figueroa, M. Gandelman, D. R. Scoles, and S. M. Pulst, “Staufen1 in Human Neurodegeneration,” Annals of Neurology 89, no. 6 (2021): 1114–1128.

[152] S. Paul, W. Dansithong, M. Gandelman, et al., “Staufen Impairs Autophagy in Neurodegeneration,” Annals of Neurology 93, no. 2 (2023): 398–416.

[153] P. Anderson, N. Kedersha, and P. Ivanov, “Stress Granules, P-Bodies and Cancer,” Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 1849, no. 7 (2015): 861–870.

[154] A. Comba, L. V. Bonnet, V. E. Goitea, M. E. Hallak, and M. R. Galiano, “Arginylated Calreticulin Increases Apoptotic Response Induced by Bortezomib in Glioma Cells,” Molecular Neurobiology 56, no. 3 (2019): 1653–1664.

[155] E. Hallacli, C. Kayatekin, S. Nazeen, et al., “The Parkinson's Disease Protein Alpha-Synuclein Is a Modulator of Processing Bodies and mRNA Stability,” Cell 185, no. 12 (2022): 2035–2056 e33.

[156] A. Simchovitz, M. Hanan, N. Niederhoffer, et al., “NEAT1 Is Overexpressed in Parkinson's Disease Substantia Nigra and Confers Drug-Inducible Neuroprotection From Oxidative Stress,” FASEB Journal 33, no. 10 (2019): 11223–11234.

[157] A. H. Fox, S. Nakagawa, T. Hirose, and C. S. Bond, “Paraspeckles: Where Long Noncoding RNA Meets Phase Separation,” Trends in Biochemical Sciences 43, no. 2 (2018): 124–135.

[158] C. Adriaens and J. C. Marine, “NEAT1-containing Paraspeckles: Central Hubs in Stress Response and Tumor Formation,” Cell Cycle 16, no. 2 (2017): 137–138.

[159] H. Shen, H. Song, S. Wang, D. Su, and Q. Sun, “NEAT1 Enhances MPP(+)-Induced Pyroptosis in a Cell Model of Parkinson's Disease via Targeting miR-5047/YAF2 Signaling,” Immunity, Inflammation and Disease 11, no. 6 (2023): e817.

[160] W. Yan, Z. Y. Chen, J. Q. Chen, and H. M. Chen, “LncRNA NEAT1 Promotes Autophagy in MPTP-Induced Parkinson's Disease Through Stabilizing PINK1 Protein,” Biochemical and Biophysical Research Communications 496, no. 4 (2018): 1019–1024.

[161] J. Chen, H. Wang, J. Wang, W. Niu, C. Deng, and M. Zhou, “LncRNA NEAT1 Enhances Glioma Progression via Regulating the miR-128-3p/ITGA5 Axis,” Molecular Neurobiology 58, no. 10 (2021): 5163–5177.

[162] F. Dong, X. Qin, B. Wang, et al., “ALKBH5 Facilitates Hypoxia-Induced Paraspeckle Assembly and IL8 Secretion to Generate an Immunosuppressive Tumor Microenvironment,” Cancer Research 81, no. 23 (2021): 5876–5888.

[163] Y. Wei, H. Luo, P. P. Yee, et al., “Paraspeckle Protein NONO Promotes TAZ Phase Separation in the Nucleus to Drive the Oncogenic Transcriptional Program,” Advanced Science 8, no. 24 (2021): e2102653.

[164] W. Zhang, S. Li, C. Li, T. Li, and Y. Huang, “Remodeling Tumor Microenvironment With Natural Products to Overcome Drug Resistance,” Frontiers in immunology 13 (2022): 1051998.

[165] D. Hanahan and M. Monje, “Cancer Hallmarks Intersect With Neuroscience in the Tumor Microenvironment,” Cancer Cell 41, no. 3 (2023): 573–580.

[166] X. Guo, Y. Pan, M. Xiong, et al., “Midkine Activation of CD8(+) T Cells Establishes a Neuron-Immune-Cancer Axis Responsible for Low-Grade Glioma Growth,” Nature Communications 11, no. 1 (2020): 2177.

[167] Y. Huang, H. Liu, J. Hu, et al., “Significant Difference of Immune Cell Fractions and Their Correlations With Differential Expression Genes in Parkinson's Disease,” Frontiers in Aging Neuroscience 13 (2021): 686066.

[168] G. P. Williams, A. M. Schonhoff, A. Sette, and C. S. Lindestam Arlehamn, “Central and Peripheral Inflammation: Connecting the Immune Responses of Parkinson's Disease,” Journal of Parkinson's Disease 12, no. s1 (2022): S129–S136.

[169] P. Riederer, T. Nagatsu, M. B. H. Youdim, M. Wulf, J. M. Dijkstra, and J. Sian-Huelsmann, “Lewy Bodies, Iron, Inflammation and Neuromelanin: Pathological Aspects Underlying Parkinson's Disease,” Journal of Neural Transmission 130, no. 5 (2023): 627–646.

[170] A. Gopinath, P. M. Mackie, L. T. Phan, M. G. Tansey, and H. Khoshbouei, “The Complex Role of Inflammation and Gliotransmitters in Parkinson's Disease,” Neurobiology of Disease 176 (2023): 105940.

[171] S. Kim, E. Pajarillo, I. Nyarko-Danquah, M. Aschner, and E. Lee, “Role of Astrocytes in Parkinson's Disease Associated With Genetic Mutations and Neurotoxicants,” Cells 12, no. 4 (2023): 622.

[172] A. N. Brandebura, A. Paumier, T. S. Onur, and N. J. Allen, “Astrocyte Contribution to Dysfunction, Risk and Progression in Neurodegenerative Disorders,” Nature Reviews Neuroscience 24, no. 1 (2023): 23–39.

[173] A. Sanchez, I. Morales, C. Rodriguez-Sabate, M. Sole-Sabater, and M. Rodriguez, “Astrocytes, a Promising Opportunity to Control the Progress of Parkinson's Disease,” Biomedicines 9, no. 10 (2021): 1341.

[174] D. Hambardzumyan, D. H. Gutmann, and H. Kettenmann, “The Role of Microglia and Macrophages in Glioma Maintenance and Progression,” Nature Neuroscience 19, no. 1 (2016): 20–27.

[175] W. Fan, Y. Song, Z. Ren, et al., “Glioma Cells Are Resistant to Inflammation‑Induced Alterations of Mitochondrial Dynamics,” International Journal of Oncology 57, no. 6 (2020): 1293–1306.

[176] R. P. Galvão and H. Zong, “Inflammation and Gliomagenesis: Bi-Directional Communication at Early and Late Stages of Tumor Progression,” Current Pathobiology Reports 1, no. 1 (2013): 19–28.

[177] J. Sim, J. W. Ahn, J. Park, et al., “Non-Canonical NLRC4 Inflammasomes in Astrocytes Contribute to Glioma Malignancy,” Inflammation Research 72, no. 4 (2023): 813–827.

[178] D. A. Putavet and P. L. J. de Keizer, “Residual Disease in Glioma Recurrence: A Dangerous Liaison With Senescence,” Cancers 13, no. 7 (2021): 1560.

[179] M. Dahlmanns, J. K. Dahlmanns, N. Savaskan, H. H. Steiner, and E. Yakubov, “Glial Glutamate Transporter-Mediated Plasticity: System x(c)(-)/xCT/SLC7A11 and EAAT1/2 in Brain Diseases,” Frontiers in Bioscience-Landmark 28, no. 3 (2023): 57.

[180] K. Connolly, M. Lehoux, R. O'Rourke, et al., “Potential Role of Chitinase-3-Like Protein 1 (CHI3L1/YKL-40) in Neurodegeneration and Alzheimer's Disease,” Alzheimer's & Dementia 19, no. 1 (2023): 9–24.

[181] F. Li, A. Liu, M. Zhao, and L. Luo, “Astrocytic Chitinase-3-Like Protein 1 in Neurological Diseases: Potential Roles and Future Perspectives,” Journal of Neurochemistry 165, no. 6 (2023): 772–790.

[182] M. Guo, J. Wang, Y. Zhao, et al., “Microglial Exosomes Facilitate α-Synuclein Transmission in Parkinson's Disease,” Brain 143, no. 5 (2020): 1476–1497.

[183] Y. Qin, J. Qiu, P. Wang, et al., “Impaired Autophagy in Microglia Aggravates Dopaminergic Neurodegeneration by Regulating NLRP3 Inflammasome Activation in Experimental Models of Parkinson's Disease,” Brain, Behavior, and Immunity 91 (2021): 324–338.

[184] J. Yuan, H. Liu, H. Zhang, T. Wang, Q. Zheng, and Z. Li, “Controlled Activation of TRPV1 Channels on Microglia to Boost Their Autophagy for Clearance of Alpha-Synuclein and Enhance Therapy of Parkinson's Disease,” Advanced Materials 34, no. 11 (2022): e2108435.

[185] Q. K. Lv, K. X. Tao, X. B. Wang, et al., “Role of α-Synuclein in Microglia: Autophagy and Phagocytosis Balance Neuroinflammation in Parkinson's Disease,” Inflammation Research 72, no. 3 (2023): 443–462.

[186] A. V. Revishchin, V. V. Parshina, and G. V. Pavlova, “The Role of Glial Cell Line-Derived Neurotrophic Factor Isoforms in Human Glial Tumors,” Voprosy neirokhirurgii imeni N.N. Burdenko 86, no. 6 (2022): 106–112.

[187] S. K. Ryan, M. Zelic, Y. Han, et al., “Microglia Ferroptosis Is Regulated by SEC24B and Contributes to Neurodegeneration,” Nature Neuroscience 26, no. 1 (2023): 12–26.

[188] B. E. Lee, H. Y. Kim, H. J. Kim, et al., “O-Glcnacylation Regulates Dopamine Neuron Function, Survival and Degeneration in Parkinson Disease,” Brain 143, no. 12 (2020): 3699–3716.

[189] X. Mao, M. T. Ou, S. S. Karuppagounder, et al., “Pathological α-Synuclein Transmission Initiated by Binding Lymphocyte-Activation Gene 3,” Science 353, no. 6307 (2016): aah3374.

[190] Y. Su, M. F. Deng, W. Xiong, et al., “MicroRNA-26a/Death-Associated Protein Kinase 1 Signaling Induces Synucleinopathy and Dopaminergic Neuron Degeneration in Parkinson's Disease,” Biological Psychiatry 85, no. 9 (2019): 769–781.

[191] E. H. Ahn, S. S. Kang, Q. Qi, X. Liu, and K. Ye, “Netrin1 Deficiency Activates MST1 via UNC5B Receptor, Promoting Dopaminergic Apoptosis in Parkinson's Disease,” Proceedings of the National Academy of Sciences 117, no. 39 (2020): 24503–24513.

[192] N. Kuzumaki, Y. Suda, C. Iwasawa, et al., “Cell-Specific Overexpression of COMT in Dopaminergic Neurons of Parkinson's Disease,” Brain 142, no. 6 (2019): 1675–1689.

[193] Y. Jia, Q. Zhao, H. Yin, et al., “Reaction-Diffusion Model-Based Research on Formation Mechanism of Neuron Dendritic Spine Patterns,” Frontiers in Neurorobotics 15 (2021): 563682.

[194] G. Sprugnoli, A. J. Golby, and E. Santarnecchi, “Newly Discovered Neuron-to-Glioma Communication: New Noninvasive Therapeutic Opportunities on the Horizon?,” Neuro-Oncology Advances 3, no. 1 (2021): vdab018.

[195] J. Yun and G. M. McKhann, “Buzz Kill: Neuronal Activity Promotes Glioma Proliferation,” Neurosurgery 77, no. 4 (2015): N14–N16.

[196] H. S. Venkatesh, T. B. Johung, V. Caretti, et al., “Neuronal Activity Promotes Glioma Growth Through Neuroligin-3 Secretion,” Cell 161, no. 4 (2015): 803–816.

[197] K. R. Taylor, T. Barron, A. Hui, et al., “Glioma Synapses Recruit Mechanisms of Adaptive Plasticity,” Nature 623, no. 7986 (2023): 366–374.

[198] N. Savaskan, Z. Fan, T. Broggini, M. Buchfelder, and I. Eyupoglu, “Neurodegeneration in the Brain Tumor Microenvironment: Glutamate in the Limelight,” Current Neuropharmacology 13, no. 2 (2015): 258–265.

[199] V. Venkataramani, “IGSF3-Mediated Potassium Dysregulation Promotes Neuronal Hyperexcitability and Glioma Progression,” Trends in Cancer 9, no. 6 (2023): 457–458.

[200] M. Miyai, T. Iwama, A. Hara, and H. Tomita, “Exploring the Vital Link Between Glioma, Neuron, and Neural Activity in the Context of Invasion,” American Journal of Pathology 193, no. 6 (2023): 669–679.

[201] E. J. Lee, Y. Choi, H. J. Lee, D. W. Hwang, and D. S. Lee, “Human Neural Stem Cell-Derived Extracellular Vesicles Protect Against Parkinson's Disease Pathologies,” Journal of Nanobiotechnology 20, no. 1 (2022): 198.

[202] W. Ni, J. Zhou, Y. Ling, et al., “Neural Stem Cell Secretome Exerts a Protective Effect on Damaged Neuron Mitochondria in Parkinson's Disease Model,” Brain Research 1790 (2022): 147978.

[203] T. Shi, J. Zhu, X. Zhang, and X. Mao, “The Role of Hypoxia and Cancer Stem Cells in Development of Glioblastoma,” Cancers 15, no. 9 (2023): 2613.

[204] X. Zhu, Y. Fang, Y. Chen, et al., “Interaction of Tumor-Associated Microglia/Macrophages and Cancer Stem Cells in Glioma,” Life Sciences 320 (2023): 121558.

[205] Q. Zhang, J. Wang, J. Zhang, and F. Liu, “Potential Functions and Therapeutic Implications of Glioma-Resident Mesenchymal Stem Cells,” Cell Biology and Toxicology 39, no. 3 (2023): 853–866.

[206] X. Yin, X. Liu, X. Xiao, et al., “Human Neural Stem Cells Repress Glioma Cell Progression in a Paracrine Manner by Downregulating the Wnt/β-Catenin Signalling Pathway,” FEBS Open Bio 13, no. 9 (2023): 1772–1788.

[207] S. L. Q. Khor, K. Y. Ng, R. Y. Koh, and S. M. Chye, “Blood-Brain Barrier and Neurovascular Unit Dysfunction in Parkinson's Disease: From Clinical Insights to Pathogenic Mechanisms and Novel Therapeutic Approaches,” CNS & Neurological Disorders - Drug Targets 23, no. 3 (2024): 315–330.

[208] E. E. Abrahamson and M. D. Ikonomovic, “Brain Injury-Induced Dysfunction of the Blood Brain Barrier as a Risk for Dementia,” Experimental Neurology 328 (2020): 113257.

[209] X. Gao, Q. Yue, Y. Liu, et al., “Image-Guided Chemotherapy With Specifically Tuned Blood Brain Barrier Permeability in Glioma Margins,” Theranostics 8, no. 11 (2018): 3126–3137.

[210] I. Pediaditakis, K. R. Kodella, D. V. Manatakis, et al., “Modeling Alpha-Synuclein Pathology in a Human Brain-Chip to Assess Blood-Brain Barrier Disruption,” Nature Communications 12, no. 1 (2021): 5907.

[211] G. Lan, P. Wang, R. B. Chan, et al., “Astrocytic VEGFA: An Essential Mediator in Blood-Brain-Barrier Disruption in Parkinson's Disease,” GLIA 70, no. 2 (2022): 337–353.

[212] A. de Rus Jacquet, M. Alpaugh, H. L. Denis, et al., “The Contribution of Inflammatory Astrocytes to BBB Impairments in a Brain-Chip Model of Parkinson's Disease,” Nature Communications 14, no. 1 (2023): 3651.

[213] S. Al-Bachari, J. H. Naish, G. J. M. Parker, H. C. A. Emsley, and L. M. Parkes, “Blood-Brain Barrier Leakage Is Increased in Parkinson's Disease,” Frontiers in Physiology 11 (2020): 593026.

[214] Z. Ruan, D. Zhang, R. Huang, et al., “Microglial Activation Damages Dopaminergic Neurons Through MMP-2/-9-Mediated Increase of Blood-Brain Barrier Permeability in a Parkinson's Disease Mouse Model,” International Journal of Molecular Sciences 23, no. 5 (2022): 2793.

[215] J. R. Kane, “The Role of Brain Vasculature in Glioblastoma,” Molecular Neurobiology 56, no. 9 (2019): 6645–6653.

[216] K. Jin, P. M. Brennan, M. T. C. Poon, J. D. Figueroa, and C. L. M. Sudlow, “Impact of Tumour Characteristics and Cancer Treatment on Cerebrovascular Mortality After Glioma Diagnosis: Evidence From a Population-Based Cancer Registry,” Frontiers in Oncology 12 (2022): 1025398.

[217] W. Huang, K. M. Ramsey, B. Marcheva, and J. Bass, “Circadian Rhythms, Sleep, and Metabolism,” Journal of Clinical Investigation 121, no. 6 (2011): 2133–2141.

[218] A. Patke, M. W. Young, and S. Axelrod, “Molecular Mechanisms and Physiological Importance of Circadian Rhythms,” Nature Reviews Molecular Cell Biology 21, no. 2 (2020): 67–84.

[219] J. Y. Liu, J. Xue, F. Wang, Y. L. Wang, and W. L. Dong, “α-Synuclein-Induced Destabilized BMAL1 mRNA Leads to Circadian Rhythm Disruption in Parkinson's Disease,” Neurotoxicity Research 41, no. 2 (2023): 177–186.

[220] Z. Wang and G. Chen, “Insights About Circadian Clock in Glioma: From Molecular Pathways to Therapeutic Drugs,” CNS Neuroscience & Therapeutics 28, no. 12 (2022): 1930–1941.

[221] L. Zhou, Z. Zhang, E. Nice, C. Huang, W. Zhang, and Y. Tang, “Circadian Rhythms and Cancers: The Intrinsic Links and Therapeutic Potentials,” Journal of Hematology & Oncology 15, no. 1 (2022): 21.

[222] L. Zhu, Q. Wang, Y. Hu, and F. Wang, “The Circadian Gene Per1 Plays an Important Role in Radiation-Induced Apoptosis and DNA Damage in Glioma,” Asian Pacific Journal of Cancer Prevention 20, no. 7 (2019): 2195–2201.

[223] Y. Xiang, J. Huang, Y. Wang, et al., “Evaluating the Genetic Role of Circadian Clock Genes in Parkinson's Disease,” Molecular Neurobiology 60, no. 5 (2023): 2729–2736.

[224] T. Li, C. Cheng, C. Jia, et al., “Peripheral Clock System Abnormalities in Patients With Parkinson's Disease,” Frontiers in Aging Neuroscience 13 (2021): 736026.

[225] Z. Li, Y. Li, X. Xu, J. Gu, H. Chen, and Y. Gui, “Exosomes Rich in Wnt5 Improved Circadian Rhythm Dysfunction via Enhanced PPARγ Activity in the 6-Hydroxydopamine Model of Parkinson's Disease,” Neuroscience Letters 802 (2023): 137139.

[226] B. W. Kristensen, L. P. Priesterbach-Ackley, J. K. Petersen, and P. Wesseling, “Molecular Pathology of Tumors of the Central Nervous System,” Annals of Oncology 30, no. 8 (2019): 1265–1278.

[227] R. Jan, S. Asif, S. Asaf, et al., “Melatonin Alleviates Arsenic (As) Toxicity in Rice Plants via Modulating Antioxidant Defense System and Secondary Metabolites and Reducing Oxidative Stress,” Environmental Pollution 318 (2023): 120868.

[228] D. Buonfiglio, D. L. Hummer, A. Armstrong, J. Christopher Ehlen, and J. P. DeBruyne, “Angelman Syndrome and Melatonin: What Can They Teach Us about Sleep Regulation,” Journal of Pineal Research 69, no. 4 (2020): e12697.

[229] X. Hu, J. Li, X. Wang, et al., “Neuroprotective Effect of Melatonin on Sleep Disorders Associated With Parkinson's Disease,” Antioxidants 12, no. 2 (2023): 396.

[230] Y. Liu, L. Niu, X. Liu, C. Cheng, and W. Le, “Recent Progress in Non-Motor Features of Parkinson's Disease With a Focus on Circadian Rhythm Dysregulation,” Neuroscience Bulletin 37, no. 7 (2021): 1010–1024.

[231] A. Borah and K. P. Mohanakumar, “Melatonin Inhibits 6-Hydroxydopamine Production in the Brain to Protect Against Experimental Parkinsonism in Rodents,” Journal of Pineal Research 47, no. 4 (2009): 293–300.

[232] J. León, D. Acuña-Castroviejo, G. Escames, D. X. Tan, and R. J. Reiter, “Melatonin Mitigates Mitochondrial Malfunction,” Journal of Pineal Research 38, no. 1 (2005): 1–9.

[233] C. Chen, C. Yang, J. Wang, et al., “Melatonin Ameliorates Cognitive Deficits Through Improving Mitophagy in a Mouse Model of Alzheimer's Disease,” Journal of Pineal Research 71, no. 4 (2021): e12774.

[234] A. Jauhari, S. V. Baranov, Y. Suofu, et al., “Melatonin Inhibits Cytosolic Mitochondrial DNA-Induced Neuroinflammatory Signaling in Accelerated Aging and Neurodegeneration,” Journal of Clinical Investigation 130, no. 6 (2020): 3124–3136.

[235] L. Y. Su, H. Li, L. Lv, et al., “Melatonin Attenuates MPTP-Induced Neurotoxicity via Preventing CDK5-Mediated Autophagy and SNCA/α-Synuclein Aggregation,” Autophagy 11, no. 10 (2015): 1745–1759.

[236] E. Moretti, G. Favero, L. F. Rodella, and R. Rezzani, “Melatonin's Antineoplastic Potential Against Glioblastoma,” Cells 9, no. 3 (2020): 599.

[237] G. Anderson, “The Effects of Melatonin on Signaling Pathways and Molecules Involved in Glioma: Melatonin and Glioblastoma: Pathophysiology and Treatment,” Fundamental & Clinical Pharmacology 34, no. 2 (2020): 189–191.

[238] B. I. Fernandez-Gil, A. Otamendi-Lopez, A. Bechtle, et al., “Melatonin Treatment Triggers Metabolic and Intracellular pH Imbalance in Glioblastoma,” Cells 11, no. 21 (2022): 3467.

[239] E. Angelopoulou, A. Bougea, Y. N. Paudel, V. E. Georgakopoulou, S. G. Papageorgiou, and C. Piperi, “Genetic Insights Into the Molecular Pathophysiology of Depression in Parkinson's Disease,” Medicina 59, no. 6 (2023): 1138.

[240] J. Zhang, Z. Guo, Q. Xie, C. Zhong, X. Gao, and Q. Yang, “Tryptophan Hydroxylase 1 Drives Glioma Progression by Modulating the Serotonin/L1CAM/NF-κB Signaling Pathway,” BMC Cancer 22, no. 1 (2022): 457.

[241] A. Maillet, P. Krack, E. Lhommée, et al., “The Prominent Role of Serotonergic Degeneration in Apathy, Anxiety and Depression in De Novo Parkinson's Disease,” Brain 139, no. Pt 9 (2016): 2486–2502.

[242] M. J. Armstrong and M. S. Okun, “Diagnosis and Treatment of Parkinson Disease: A Review,” Journal of the American Medical Association 323, no. 6 (2020): 548–560.

[243] R. Yang, S. Ye, S. Zhang, et al., “Serotonin and Dopamine Depletion in Distinct Brain Regions May Cause Anxiety in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Treated Mice as a Model of Early Parkinson's Disease,” Neuroreport 34, no. 11 (2023): 551–559.

[244] M. A. Samizadeh, H. Fallah, M. Toomarisahzabi, et al., “Parkinson's Disease: A Narrative Review on Potential Molecular Mechanisms of Sleep Disturbances, REM Behavior Disorder, and Melatonin,” Brain Sciences 13, no. 6 (2023): 914.

[245] S. P. Caragher, R. R. Hall, R. Ahsan, and A. U. Ahmed, “Monoamines in Glioblastoma: Complex Biology With Therapeutic Potential,” Neuro-Oncology 20, no. 8 (2018): 1014–1025.

[246] K. Morita, T. Gotohda, H. Arimochi, M. S. Lee, and S. Her, “Histone Deacetylase Inhibitors Promote Neurosteroid-Mediated Cell Differentiation and Enhance Serotonin-Stimulated Brain-Derived Neurotrophic Factor Gene Expression in Rat C6 Glioma Cells,” Journal of Neuroscience Research 87, no. 11 (2009): 2608–2614.

[247] F. Courant, M. Maravat, W. Chen, et al., “Expression of the Human Serotonin 5-HT(7) Receptor Rescues Phenotype Profile and Restores Dysregulated Biomarkers in a Drosophila melanogaster Glioma Model,” Cells 11, no. 8 (2022): 1281.

[248] G. Bocheva, D. Bakalov, P. Iliev, and R. Tafradjiiska-Hadjiolova, “The Vital Role of Melatonin and Its Metabolites in the Neuroprotection and Retardation of Brain Aging,” International Journal of Molecular Sciences 25, no. 10 (2024): 5122.

[249] A. Mafi, M. Rezaee, N. Hedayati, et al., “Melatonin and 5-Fluorouracil Combination Chemotherapy: Opportunities and Efficacy in Cancer Therapy,” Cell Communication and Signaling 21, no. 1 (2023): 33.

[250] J. F. Fu, M. Matarazzo, J. McKenzie, et al., “Serotonergic System Impacts Levodopa Response in Early Parkinson's and Future Risk of Dyskinesia,” Movement Disorders 36, no. 2 (2021): 389–397.

[251] S. Karmakar and G. Lal, “Role of Serotonin Receptor Signaling in Cancer Cells and Anti-Tumor Immunity,” Theranostics 11, no. 11 (2021): 5296–5312.

[252] M. Friedrich, R. Sankowski, L. Bunse, et al., “Tryptophan Metabolism Drives Dynamic Immunosuppressive Myeloid States in IDH-Mutant Gliomas,” Nature Cancer 2, no. 7 (2021): 723–740.

[253] D. González Esquivel, D. Ramírez-Ortega, B. Pineda, N. Castro, C. Ríos, and V. Pérez de la Cruz, “Kynurenine Pathway Metabolites and Enzymes Involved in Redox Reactions,” Neuropharmacology 112, no. Pt B (2017): 331–345.

[254] Z. W. Ye, J. Zhang, D. M. Townsend, and K. D. Tew, “Oxidative Stress, Redox Regulation and Diseases of Cellular Differentiation,” Biochimica et Biophysica Acta (BBA) - General Subjects 1850, no. 8 (2015): 1607–1621.

[255] P. H. G. M. Willems, R. Rossignol, C. E. J. Dieteren, M. P. Murphy, and W. J. H. Koopman, “Redox Homeostasis and Mitochondrial Dynamics,” Cell Metabolism 22, no. 2 (2015): 207–218.

[256] H. J. Forman and H. Zhang, “Targeting Oxidative Stress in Disease: Promise and Limitations of Antioxidant Therapy,” Nature Reviews Drug Discovery 20, no. 9 (2021): 689–709.

[257] E. Obrador, R. Salvador-Palmer, R. López-Blanch, A. Jihad-Jebbar, S. L. Vallés, and J. M. Estrela, “The Link Between Oxidative Stress, Redox Status, Bioenergetics and Mitochondria in the Pathophysiology of ALS,” International Journal of Molecular Sciences 22, no. 12 (2021): 6352.

[258] J. M. C. Gutteridge and B. Halliwell, “Mini-Review: Oxidative Stress, Redox Stress or Redox Success?,” Biochemical and Biophysical Research Communications 502, no. 2 (2018): 183–186.

[259] C. Lismont, M. Nordgren, P. P. Van Veldhoven, and M. Fransen, “Redox Interplay Between Mitochondria and Peroxisomes,” Frontiers in Cell and Developmental Biology 3 (2015): 35.

[260] S. J. Storr, C. M. Woolston, Y. Zhang, and S. G. Martin, “Redox Environment, Free Radical, and Oxidative DNA Damage,” Antioxidants & Redox Signaling 18, no. 18 (2013): 2399–2408.

[261] A. Kaur, P. T. Van, C. R. Busch, et al., “Coordination of Frontline Defense Mechanisms under Severe Oxidative Stress,” Molecular Systems Biology 6 (2010): 393.

[262] J. S. Bhatti, G. K. Bhatti, and P. H. Reddy, “Mitochondrial Dysfunction and Oxidative Stress in Metabolic Disorders—A Step Towards Mitochondria Based Therapeutic Strategies,” Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1863, no. 5 (2017): 1066–1077.

[263] C. Gemma, J. Vila, A. Bachstetter, and P. C. Bickford, “ Oxidative Stress and the Aging Brain: From Theory to Prevention,” in Brain Aging: Models, Methods, and Mechanisms, eds. D. R. Riddle (CRC Press/Taylor & Francis, 2007), 215–236.

[264] S. Li, R. Baiyun, Z. Lv, et al., “Exploring the Kidney Hazard of Exposure to Mercuric Chloride in Mice:Disorder of Mitochondrial Dynamics Induces Oxidative Stress and Results in Apoptosis,” Chemosphere 234 (2019): 822–829.

[265] K. M. Stepien, R. Heaton, S. Rankin, et al., “Evidence of Oxidative Stress and Secondary Mitochondrial Dysfunction in Metabolic and Non-Metabolic Disorders,” Journal of Clinical Medicine 6, no. 7 (2017): 71.

[266] Z. X. Wang, Y. L. Li, J. L. Pu, and B. R. Zhang, “DNA Damage-Mediated Neurotoxicity in Parkinson's Disease,” International Journal of Molecular Sciences 24, no. 7 (2023): 6313.

[267] M. Al Shahrani, S. Heales, I. Hargreaves, and M. Orford, “Oxidative Stress: Mechanistic Insights Into Inherited Mitochondrial Disorders and Parkinson's Disease,” Journal of Clinical Medicine 6, no. 11 (2017): 100.

[268] S. Shadfar, S. Parakh, M. S. Jamali, and J. D. Atkin, “Redox Dysregulation as a Driver for DNA Damage and Its Relationship to Neurodegenerative Diseases,” Translational Neurodegeneration 12, no. 1 (2023): 18.

[269] V. Sosa, T. Moliné, R. Somoza, R. Paciucci, H. Kondoh, and M. E. LLeonart, “Oxidative Stress and Cancer: An Overview,” Ageing Research Reviews 12, no. 1 (2013): 376–390.

[270] J. Cadet, J. L. Ravanat, M. TavernaPorro, H. Menoni, and D. Angelov, “Oxidatively Generated Complex DNA Damage: Tandem and Clustered Lesions,” Cancer Letters 327, no. 1–2 (2012): 5–15.

[271] L. Cui, W. Ye, E. G. Prestwich, et al., “Comparative Analysis of Four Oxidized Guanine Lesions From Reactions of DNA With Peroxynitrite, Singlet Oxygen, and γ-Radiation,” Chemical Research in Toxicology 26, no. 2 (2013): 195–202.

[272] C. G. Fraga, M. K. Shigenaga, J. W. Park, P. Degan, and B. N. Ames, “Oxidative Damage to DNA During Aging: 8-Hydroxy-2'-Deoxyguanosine in Rat Organ DNA and Urine,” Proceedings of the National Academy of Sciences 87, no. 12 (1990): 4533–4537.

[273] J. Tong, G. Rathitharan, J. H. Meyer, et al., “Brain Monoamine Oxidase B and A in Human Parkinsonian Dopamine Deficiency Disorders,” Brain 140, no. 9 (2017): 2460–2474.

[274] E. O. Olufunmilayo, M. B. Gerke-Duncan, and R. M. D. Holsinger, “Oxidative Stress and Antioxidants in Neurodegenerative Disorders,” Antioxidants 12, no. 2 (2023): 517.

[275] S. Gonfloni, E. Maiani, C. Di Bartolomeo, M. Diederich, and G. Cesareni, “Oxidative Stress, DNA Damage, and c-Abl Signaling: At the Crossroad in Neurodegenerative Diseases?,” International Journal of Cell Biology 2012 (2012): 683097.

[276] Y. L. Li, Z. X. Wang, C. Z. Ying, B. R. Zhang, and J. L. Pu, “Decoding the Role of Familial Parkinson's Disease-Related Genes in DNA Damage and Repair,” Aging and Disease 13, no. 5 (2022): 1405–1412.

[277] C. P. Gonzalez-Hunt and L. H. Sanders, “DNA Damage and Repair in Parkinson's Disease: Recent Advances and New Opportunities,” Journal of Neuroscience Research 99, no. 1 (2021): 180–189.

[278] K. C. Luk, “Oxidative Stress and α-Synuclein Conspire in Vulnerable Neurons to Promote Parkinson's Disease Progression,” Journal of Clinical Investigation 129, no. 9 (2019): 3530–3531.

[279] C. Hacioglu, F. Kar, S. Kacar, V. Sahinturk, and G. Kanbak, “Bexarotene Inhibits Cell Proliferation by Inducing Oxidative Stress, DNA Damage and Apoptosis via PPARγ/NF-κB Signaling Pathway in C6 Glioma Cells,” Medical Oncology 38, no. 3 (2021): 31.

[280] R. P. Ostrowski and E. B. Pucko, “Harnessing Oxidative Stress for Anti-Glioma Therapy,” Neurochemistry International 154 (2022): 105281.

[281] I. Graiet, H. Hamdi, S. Abid-Essefi, and J. Eyer, “Fludioxonil, a Phenylpyrrol Pesticide, Induces Cytoskeleton Disruption, DNA Damage and Apoptosis via Oxidative Stress on Rat Glioma Cells,” Food and Chemical Toxicology 170 (2022): 113464.

[282] W. Cao, X. Zhai, J. Ma, et al., “Natural Borneol Sensitizes Human Glioma Cells to Cisplatin-Induced Apoptosis by Triggering ROS-Mediated Oxidative Damage and Regulation of MAPKs and PI3K/AKT Pathway,” Pharmaceutical Biology 58, no. 1 (2020): 72–79.

[283] H. Wu, X. Fu, W. Cao, et al., “Induction of Apoptosis in Human Glioma Cells by Fucoxanthin via Triggering of ROS-Mediated Oxidative Damage and Regulation of Mapks and PI3K-AKT Pathways,” Journal of Agricultural and Food Chemistry 67, no. 8 (2019): 2212–2219.

[284] Y. Soh, “Oxidative Dna Damage and Glioma Cell Death Induced by Tetrahydropapaveroline,” Mutation Research/Reviews in Mutation Research 544, no. 2–3 (2003): 129–142.

[285] A. Jurcau, “Insights into the Pathogenesis of Neurodegenerative Diseases: Focus on Mitochondrial Dysfunction and Oxidative Stress,” International Journal of Molecular Sciences 22, no. 21 (2021): 11847.

[286] R. E. Musgrove, M. Helwig, E. J. Bae, et al., “Oxidative Stress in Vagal Neurons Promotes Parkinsonian Pathology and Intercellular α-Aynuclein Transfer,” Journal of Clinical Investigation 129, no. 9 (2019): 3738–3753.

[287] S. J. Won, R. Fong, N. Butler, et al., “Neuronal Oxidative Stress Promotes Alpha-Synuclein Aggregation In Vivo,” Antioxidants (Basel) 11, no. 12 (2022): 100.

[288] M. V. Rao, S. Darji, P. H. Stavrides, et al., “Autophagy Is a Novel Pathway for Neurofilament Protein Degradation In Vivo,” Autophagy 19, no. 4 (2023): 1277–1292.

[289] G. A. Collins and A. L. Goldberg, “The Logic of the 26S Proteasome,” Cell 169, no. 5 (2017): 792–806.

[290] E. V. Rusilowicz-Jones, S. Urbé, and M. J. Clague, “Protein Degradation on the Global Scale,” Molecular Cell 82, no. 8 (2022): 1414–1423.

[291] N. Joshi, A. Raveendran, and S. Nagotu, “Chaperones and Proteostasis: Role in Parkinson's Disease,” Diseases 8, no. 2 (2020): 24.

[292] A. E. Ahmed, S. Jacob, A. A. Nagy, and A. B. Abdel-Naim, “Dibromoacetonitrile-Induced Protein Oxidation and Inhibition of Proteasomal Activity in Rat Glioma Cells,” Toxicology Letters 179, no. 1 (2008): 29–33.

[293] N. Nakayama, S. Yamaguchi, Y. Sasaki, and T. Chikuma, “Hydrogen Peroxide-Induced Oxidative Stress Activates Proteasomal Trypsin-Like Activity in Human U373 Glioma Cells,” Journal of Molecular Neuroscience 58, no. 2 (2016): 297–305.

[294] M. Y. Ali, C. E. Griguer, S. Flor, and C. R. Oliva, “Mitoferrin-1 Promotes Proliferation and Abrogates Protein Oxidation via the Glutathione Pathway in Glioblastoma,” Antioxidants 12, no. 2 (2023): 349.

[295] A. Santoro, G. Mattace Raso, S. Taliani, et al., “Tspo-Ligands Prevent Oxidative Damage and Inflammatory Response in C6 Glioma Cells by Neurosteroid Synthesis,” European Journal of Pharmaceutical Sciences 88 (2016): 124–131.

[296] P. R. Angelova, N. Esteras, and A. Y. Abramov, “Mitochondria and Lipid Peroxidation in the Mechanism of Neurodegeneration: Finding Ways for Prevention,” Medicinal Research Reviews 41, no. 2 (2021): 770–784.

[297] M. W. Park, H. W. Cha, J. Kim, et al., “NOX4 Promotes Ferroptosis of Astrocytes by Oxidative Stress-Induced Lipid Peroxidation via the Impairment of Mitochondrial Metabolism in Alzheimer's Diseases,” Redox Biology 41 (2021): 101947.

[298] M. K. Foret, R. Lincoln, S. Do Carmo, A. C. Cuello, and G. Cosa, “Connecting the ‘Dots’: From Free Radical Lipid Autoxidation to Cell Pathology and Disease,” Chemical Reviews 120, no. 23 (2020): 12757–12787.

[299] E. Niedzielska, I. Smaga, M. Gawlik, et al., “Oxidative Stress in Neurodegenerative Diseases,” Molecular Neurobiology 53, no. 6 (2016): 4094–4125.

[300] Y. N. Jiang, Y. Z. Guo, D. H. Lu, et al., “Tianma Gouteng Granules Decreases the Susceptibility of Parkinson's Disease by Inhibiting ALOX15-Mediated Lipid Peroxidation,” Journal of Ethnopharmacology 256 (2020): 112824.

[301] C. Gorrini, I. S. Harris, and T. W. Mak, “Modulation of Oxidative Stress as an Anticancer Strategy,” Nature Reviews Drug Discovery 12, no. 12 (2013): 931–947.

[302] H. Sharma, N. Sharma, and S. S. A. An, “Black Pepper (Piper nigrum) Alleviates Oxidative Stress, Exerts Potential Anti-Glycation and Anti-AChE Activity: A Multitargeting Neuroprotective Agent Against Neurodegenerative Diseases,” Antioxidants 12, no. 5 (2023): 1089.

[303] P. Sienes Bailo, E. Llorente Martín, P. Calmarza, et al., “The Role of Oxidative Stress in Neurodegenerative Diseases and Potential Antioxidant Therapies,” Advances in Laboratory Medicine/Avances en Medicina de Laboratorio 3, no. 4 (2022): 342–350.

[304] H. Kahroba, B. Ramezani, H. Maadi, M. R. Sadeghi, H. Jaberie, and F. Ramezani, “The Role of Nrf2 in Neural Stem/Progenitors Cells: From Maintaining Stemness and Self-Renewal to Promoting Differentiation Capability and Facilitating Therapeutic Application in Neurodegenerative Disease,” Ageing Research Reviews 65 (2021): 101211.

[305] E. Yakubov, T. Eibl, A. Hammer, M. Holtmannspötter, N. Savaskan, and H. H. Steiner, “Therapeutic Potential of Selenium in Glioblastoma,” Frontiers in Neuroscience 15 (2021): 666679.

[306] M. Szeliga and R. Rola, “Menadione Potentiates Auranofin-Induced Glioblastoma Cell Death,” International Journal of Molecular Sciences 23, no. 24 (2022): 15712.

[307] C. Hacioglu and F. Kar, “Capsaicin Induces Redox Imbalance and Ferroptosis Through ACSL4/GPx4 Signaling Pathways in U87-MG and U251 Glioblastoma Cells,” Metabolic Brain Disease 38, no. 2 (2023): 393–408.

[308] E. R. Jackson, R. J. Duchatel, D. E. Staudt, et al., “ONC201 in Combination With Paxalisib for the Treatment of H3K27-Altered Diffuse Midline Glioma,” Cancer Research 83, no. 14 (2023): 2421–2437.

[309] T. Jin, Y. Zhang, B. O. A. Botchway, et al., “Curcumin Can Improve Parkinson's Disease via Activating BDNF/PI3k/Akt Signaling Pathways,” Food and Chemical Toxicology 164 (2022): 113091.

[310] T. C. Chen, J. Y. Chuang, C. Y. Ko, et al., “AR Ubiquitination Induced by the Curcumin Analog Suppresses Growth of Temozolomide-Resistant Glioblastoma Through Disrupting GPX4-Mediated Redox Homeostasis,” Redox Biology 30 (2020): 101413.

[311] M. A. Altinoz, I. Elmaci, A. Hacimuftuoglu, A. Ozpinar, E. Hacker, and A. Ozpinar, “PPARdelta and Its Ligand Erucic Acid May Act Anti-Tumoral, Neuroprotective, and Myelin Protective in Neuroblastoma, Glioblastoma, and Parkinson's Disease,” Molecular Aspects of Medicine 78 (2021): 100871.

[312] E. M. M. Quigley, “Microbiota-Brain-Gut Axis and Neurodegenerative Diseases,” Current Neurology and Neuroscience Reports 17, no. 12 (2017): 94.

[313] X. Liu, Y. Chen, S. Zhang, and L. Dong, “Gut Microbiota-Mediated Immunomodulation in Tumor,” Journal of Experimental & Clinical Cancer Research 40, no. 1 (2021): 221.

[314] S. Y. Zheng, H. X. Li, R. C. Xu, et al., “Potential Roles of Gut Microbiota and Microbial Metabolites in Parkinson's Disease,” Ageing Research Reviews 69 (2021): 101347.

[315] T. R. Sampson, J. W. Debelius, T. Thron, et al., “Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease,” Cell 167, no. 6 (2016): 1469–1480.e12.

[316] M. F. Sun and Y. Q. Shen, “Dysbiosis of Gut Microbiota and Microbial Metabolites in Parkinson's Disease,” Ageing Research Reviews 45 (2018): 53–61.

[317] J. C. Claudino Dos Santos, M. P. P. Lima, G. A. C. Brito, and G. S. B. Viana, “Role of Enteric Glia and Microbiota-Gut-Brain Axis in Parkinson Disease Pathogenesis,” Ageing Research Reviews 84 (2023): 101812.

[318] Y. Lyu, H. Yang, and L. Chen, “Metabolic Regulation on the Immune Environment of Glioma Through Gut Microbiota,” Seminars in Cancer Biology 86, no. Pt 2 (2022): 990–997.

[319] G. D'Alessandro, C. Lauro, D. Quaglio, et al., “Neuro-Signals From Gut Microbiota: Perspectives for Brain Glioma,” Cancers 13, no. 11 (2021): 2810.

[320] R. Mancusi and M. Monje, “The Neuroscience of Cancer,” Nature 618, no. 7965 (2023): 467–479.

[321] D. Yaniv, B. Mattson, S. Talbot, F. O. Gleber-Netto, and M. Amit, “Targeting the Peripheral Neural-Tumour Microenvironment for Cancer Therapy,” Nature Reviews Drug Discovery 23, no. 10 (2024): 780–796.

[322] Q. Huang, B. Hu, P. Zhang, et al., “Neuroscience of Cancer: Unraveling the Complex Interplay Between the Nervous System, the Tumor and the Tumor Immune Microenvironment,” Molecular cancer 24, no. 1 (2025): 24.

[323] W. L. Hwang, E. N. Perrault, A. Birbrair, et al., “Integrating Priorities at the Intersection of Cancer and Neuroscience,” Cancer Cell 43, no. 1 (2025): 1–5.

[324] Z. K. Dong, Y. F. Wang, W. P. Li, and W. L. Jin, “Neurobiology of Cancer: Adrenergic Signaling and Drug Repurposing,” Pharmacology & Therapeutics 264 (2024): 108750.

[325] T. Zhang, F. Zhao, Y. Lin, et al., “Integrated Analysis of Single-Cell and Bulk Transcriptomics Develops a Robust Neuroendocrine Cell-Intrinsic Signature to Predict Prostate Cancer Progression,” Theranostics 14, no. 3 (2024): 1065–1080.

[326] B. Ni, Y. Yin, Z. Li, J. Wang, X. Wang, and K. Wang, “Crosstalk Between Peripheral Innervation and Pancreatic Ductal Adenocarcinoma,” Neuroscience Bulletin 39, no. 11 (2023): 1717–1731.

[327] K. Wang, B. Ni, Y. Xie, et al., “Nociceptor Neurons Promote Pdac Progression and Cancer Pain by Interaction With Cancer-Associated Fibroblasts and Suppression of Natural Killer Cells,” Cell Research 35, no. 5 (2025): 362–380.

[328] Y. Zhang, Q. Liao, X. Wen, et al., “Hijacking of the Nervous System in Cancer: Mechanism and Therapeutic Targets,” Molecular Cancer 24, no. 1 (2025): 44.

[329] S. Heuer and F. Winkler, “Glioblastoma Revisited: From Neuronal-Like Invasion to Pacemaking,” Trends in Cancer 9, no. 11 (2023): 887–896.

[330] S. Brem, “Vagus Nerve Stimulation: Novel Concept for the Treatment of Glioblastoma and Solid Cancers by Cytokine (interleukin-6) Reduction, Attenuating the SASP, Enhancing Tumor Immunity,” Brain, Behavior, & Immunity - Health 42 (2024): 100859.

[331] S. Vatansever, A. Schlessinger, D. Wacker, et al., “Artificial Intelligence and Machine Learning-Aided Drug Discovery in Central Nervous System Diseases: State-of-the-Arts and Future Directions,” Medicinal Research Reviews 41, no. 3 (2021): 1427–1473.

[332] J. Maciejowski and T. Mohamed, “APOBEC3 Upregulation Drives Gemcitabine Resistance,” Nature Cancer 5, no. 6 (2024): 818–820.

[333] A. T. Meger, M. A. Spence, M. Sandhu, et al., “Rugged Fitness Landscapes Minimize Promiscuity in the Evolution of Transcriptional Repressors,” Cell Systems 15, no. 4 (2024): 374–387.e6.

[334] M. Amit, C. Anastasaki, R. Dantzer, et al., “Next Directions in the Neuroscience of Cancers Arising Outside the CNS,” Cancer Discovery 14, no. 4 (2024): 669–673.

[335] A. Salvalaggio, L. Pini, A. Bertoldo, and M. Corbetta, “Glioblastoma and Brain Connectivity: The Need for a Paradigm Shift,” Lancet Neurology 23, no. 7 (2024): 740–748.

[336] P. Shamshiripour, M. Rahnama, M. Nikoobakht, V. F. Rad, A. R. Moradi, and D. Ahmadvand, “Extracellular Vesicles Derived From Dendritic Cells Loaded With VEGF-A siRNA and Doxorubicin Reduce Glioma Angiogenesis In Vitro,” Journal of Controlled Release 369 (2024): 128–145.

[337] Q. Zeng, I. P. Michael, P. Zhang, et al., “Synaptic Proximity Enables Nmdar Signalling to Promote Brain Metastasis,” Nature 573, no. 7775 (2019): 526–531.

[338] E. Jung, J. Alfonso, H. Monyer, W. Wick, and F. Winkler, “Neuronal Signatures in Cancer,” International Journal of Cancer 147, no. 12 (2020): 3281–3291.

[339] F. Winkler, H. S. Venkatesh, M. Amit, et al., “Cancer Neuroscience: State of the Field, Emerging Directions,” Cell 186, no. 8 (2023): 1689–1707.

[340] L. Douw, L. C. Breedt, and M. L. M. Zimmermann, “Cancer Meets Neuroscience: The Association Between Glioma Occurrence and Intrinsic Brain Features,” Brain 146, no. 3 (2023): 803–805.

[341] V. Venkataramani, Y. Yang, M. C. Schubert, et al., “Glioblastoma Hijacks Neuronal Mechanisms for Brain Invasion,” Cell 185, no. 16 (2022): 2899–2917 e31.

[342] K. Yu, C. C. J. Lin, A. Hatcher, et al., “PIK3CA Variants Selectively Initiate Brain Hyperactivity During Gliomagenesis,” Nature 578, no. 7793 (2020): 166–171.

[343] P. González-Rodríguez, E. Zampese, K. A. Stout, et al., “Disruption of Mitochondrial Complex I Induces Progressive Parkinsonism,” Nature 599, no. 7886 (2021): 650–656.

[344] E. Gregory, R. Dugan, G. David, and Y. H. Song, “The Biology and Engineered Modeling Strategies of Cancer-Nerve Crosstalk,” Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1874, no. 2 (2020): 188406.

[345] C. Spinelli, L. Adnani, B. Meehan, et al., “Mesenchymal Glioma Stem Cells Trigger Vasectasia-Distinct Neovascularization Process Stimulated by Extracellular Vesicles Carrying EGFR,” Nature Communications 15, no. 1 (2024): 2865.

[346] Y. Hoogstrate, K. Draaisma, S. A. Ghisai, et al., “Transcriptome Analysis Reveals Tumor Microenvironment Changes In Glioblastoma,” Cancer Cell 41, no. 4 (2023): 678–692.e7.

[347] N. Khanmammadova, S. Islam, P. Sharma, and M. Amit, “Neuro-Immune Interactions and Immuno-Oncology,” Trends in Cancer 9, no. 8 (2023): 636–649.

[348] F. S. Varn, K. C. Johnson, J. Martinek, et al., “Glioma Progression Is Shaped by Genetic Evolution and Microenvironment Interactions,” Cell 185, no. 12 (2022): 2184–2199.e16.

[349] H. S. Venkatesh, W. Morishita, A. C. Geraghty, et al., “Electrical and Synaptic Integration of Glioma Into Neural Circuits,” Nature 573, no. 7775 (2019): 539–545.

[350] H. S. Venkatesh, L. T. Tam, P. J. Woo, et al., “Targeting Neuronal Activity-Regulated Neuroligin-3 Dependency in High-Grade Glioma,” Nature 549, no. 7673 (2017): 533–537.

[351] R. J. Duchatel, E. R. Jackson, S. G. Parackal, et al., “PI3K/mTOR Is a Therapeutically Targetable Genetic Dependency in Diffuse Intrinsic Pontine Glioma,” Journal of Clinical Investigation 134, no. 6 (2024): e170329.

[352] P. Jarabo, C. de Pablo, H. Herranz, F. A. Martín, and S. Casas-Tintó, “Insulin Signaling Mediates Neurodegeneration in Glioma,” Life Science Alliance 4, no. 3 (2021): e202000693.

[353] M. B. Keough and M. Monje, “Neural Signaling in Cancer,” Annual Review of Neuroscience 45 (2022): 199–221.

[354] E. Jung, J. Alfonso, M. Osswald, H. Monyer, W. Wick, and F. Winkler, “Emerging Intersections Between Neuroscience and Glioma Biology,” Nature Neuroscience 22, no. 12 (2019): 1951–1960.

[355] S. Dolma, H. J. Selvadurai, X. Lan, et al., “Inhibition of Dopamine Receptor D4 Impedes Autophagic Flux, Proliferation, and Survival of Glioblastoma Stem Cells,” Cancer Cell 29, no. 6 (2016): 859–873.

[356] W. H. Tomaszewski, J. Waibl-Polania, M. Chakraborty, et al., “Neuronal CaMKK2 Promotes Immunosuppression and Checkpoint Blockade Resistance in Glioblastoma,” Nature Communications 13, no. 1 (2022): 6483.

[357] Z. Zhang, Y. Li, X. Lv, L. Zhao, and X. Wang, “VLM Catecholaminergic Neurons Control Tumor Growth by Regulating CD8(+) T Cells,” Proceedings of the National Academy of Sciences 118, no. 28 (2021): e2103505118.

[358] M. Monje, J. C. Borniger, N. J. D'Silva, et al., “Roadmap for the Emerging Field of Cancer Neuroscience,” Cell 181, no. 2 (2020): 219–222.

[359] C. M. Zhao, Y. Hayakawa, Y. Kodama, et al., “Denervation Suppresses Gastric Tumorigenesis,” Science Translational Medicine 6, no. 250 (2014): 250ra115.

[360] C. Hutchings, J. A. Phillips, and M. B. A. Djamgoz, “Nerve Input to Tumours: Pathophysiological Consequences of a Dynamic Relationship,” Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1874, no. 2 (2020): 188411.

[361] P. Zhu, T. Lu, Z. Chen, et al., “5-Hydroxytryptamine Produced by Enteric Serotonergic Neurons Initiates Colorectal Cancer Stem Cell Self-Renewal and Tumorigenesis,” Neuron 110, no. 14 (2022): 2268–2282 e4.

[362] S. Pan, K. Yin, Z. Tang, et al., “Stimulation of Hypothalamic Oxytocin Neurons Suppresses Colorectal Cancer Progression in Mice,” eLife 10 (2021): e67535.

[363] C. Magnon, S. J. Hall, J. Lin, et al., “Autonomic Nerve Development Contributes to Prostate Cancer Progression,” Science 341, no. 6142 (2013): 1236361.

[364] R. S. Banh, D. E. Biancur, K. Yamamoto, et al., “Neurons Release Serine to Support mRNA Translation in Pancreatic Cancer,” Cell 183, no. 5 (2020): 1202–1218.e25.

[365] A. Masato, N. Plotegher, D. Boassa, and L. Bubacco, “Impaired Dopamine Metabolism in Parkinson's Disease Pathogenesis,” Molecular Neurodegeneration 14, no. 1 (2019): 35.

[366] P. Mauffrey, N. Tchitchek, V. Barroca, et al., “Progenitors From the Central Nervous System Drive Neurogenesis in Cancer,” Nature 569, no. 7758 (2019): 672–678.

[367] A. H. Zahalka, A. Arnal-Estapé, M. Maryanovich, et al., “Adrenergic Nerves Activate an Angio-Metabolic Switch in Prostate Cancer,” Science 358, no. 6361 (2017): 321–326.

[368] V. Venkataramani, D. I. Tanev, C. Strahle, et al., “Glutamatergic Synaptic Input to Glioma Cells Drives Brain Tumour Progression,” Nature 573, no. 7775 (2019): 532–538.

[369] S. J. Crowley, P. Kanel, S. Roytman, N. I. Bohnen, and B. M. Hampstead, “Basal Forebrain Integrity, Cholinergic Innervation and Cognition in Idiopathic Parkinson's Disease,” Brain 147, no. 5 (2024): 1799–1808.

[370] A. Björklund and R. A. Barker, “The Basal Forebrain Cholinergic System as Target for Cell Replacement Therapy in Parkinson's Disease,” Brain 147, no. 6 (2024): 1937–1952.

[371] B. W. Renz, T. Tanaka, M. Sunagawa, et al., “Cholinergic Signaling via Muscarinic Receptors Directly and Indirectly Suppresses Pancreatic Tumorigenesis and Cancer Stemness,” Cancer Discovery 8, no. 11 (2018): 1458–1473.

[372] A. Kamiya, Y. Hayama, S. Kato, et al., “Retracted Article: Genetic Manipulation of Autonomic Nerve Fiber Innervation and Activity and Its Effect on Breast Cancer Progression,” Nature Neuroscience 22, no. 8 (2019): 1289–1305.

[373] P. Chen, W. Wang, R. Liu, et al., “Olfactory Sensory Experience Regulates Gliomagenesis via Neuronal IGF1,” Nature 606, no. 7914 (2022): 550–556.

[374] Y. Pan, J. D. Hysinger, T. Barron, et al., “NF1 Mutation Drives Neuronal Activity-Dependent Initiation of Optic Glioma,” Nature 594, no. 7862 (2021): 277–282.

[375] E. K. Sloan, S. J. Priceman, B. F. Cox, et al., “The Sympathetic Nervous System Induces a Metastatic Switch in Primary Breast Cancer,” Cancer Research 70, no. 18 (2010): 7042–7052.

[376] X. Guo, W. Qiu, C. Wang, et al., “Neuronal Activity Promotes Glioma Progression by Inducing Proneural-to-Mesenchymal Transition in Glioma Stem Cells,” Cancer Research 84, no. 3 (2024): 372–387.

[377] D. S. L. Harwood, V. Pedersen, N. S. Bager, et al., “Glioblastoma Cells Increase Expression of Notch Signaling and Synaptic Genes Within Infiltrated Brain Tissue,” Nature Communications 15, no. 1 (2024): 7857.

[378] E. Huang-Hobbs, Y. T. Cheng, Y. Ko, et al., “Remote Neuronal Activity Drives Glioma Progression Through SEMA4F,” Nature 619, no. 7971 (2023): 844–850.

[379] L. Caló, E. Hidari, M. Wegrzynowicz, et al., “CSPα Reduces Aggregates and Rescues Striatal Dopamine Release in α-Synuclein Transgenic Mice,” Brain 144, no. 6 (2021): 1661–1669.

[380] N. J. Diederich, T. Uchihara, S. Grillner, and C. G. Goetz, “The Evolution-Driven Signature of Parkinson's Disease,” Trends in Neurosciences 43, no. 7 (2020): 475–492.

[381] L. Merino-Galán, H. Jimenez-Urbieta, M. Zamarbide, et al., “Striatal Synaptic Bioenergetic and Autophagic Decline in Premotor Experimental Parkinsonism,” Brain 145, no. 6 (2022): 2092–2107.

[382] R. Spelat, N. Jihua, C. A. Sánchez Triviño, et al., “The Dual Action of Glioma-Derived Exosomes on Neuronal Activity: Synchronization and Disruption of Synchrony,” Cell Death & Disease 13, no. 8 (2022): 705.

[383] Y. Yang, M. C. Schubert, T. Kuner, W. Wick, F. Winkler, and V. Venkataramani, “Brain Tumor Networks in Diffuse Glioma,” Neurotherapeutics 19, no. 6 (2022): 1832–1843.

[384] K. R. Taylor and M. Monje, “Invasive Glioma Cells: The Malignant Pioneers That Follow the Current,” Cell 185, no. 16 (2022): 2846–2848.

[385] Q. Huang, C. Lian, Y. Dong, et al., “SNAP25 Inhibits Glioma Progression by Regulating Synapse Plasticity via GLS-Mediated Glutaminolysis,” Frontiers in Oncology 11 (2021): 698835.

[386] N. Kang, S. Son, S. Min, et al., “Stimuli-Responsive Ferroptosis for Cancer Therapy,” Chemical Society Reviews 52, no. 12 (2023): 3955–3972.

[387] W. Xie, S. Agarwal, and J. Yu, “Ferroptosis: The Vulnerability Within a Cancer Monster,” Journal of Clinical Investigation 133, no. 10 (2023): e170027.

[388] R. Gupta, R. K. Ambasta, and K. Pravir Kumar, “Autophagy and Apoptosis Cascade: Which Is More Prominent in Neuronal Death?,” Cellular and Molecular Life Sciences 78, no. 24 (2021): 8001–8047.

[389] J. Debnath, N. Gammoh, and K. M. Ryan, “Autophagy and Autophagy-Related Pathways in Cancer,” Nature Reviews Molecular Cell Biology 24, no. 8 (2023): 560–575.

[390] B. A. Carneiro and W. S. El-Deiry, “Targeting Apoptosis in Cancer Therapy,” Nature Reviews Clinical Oncology 17, no. 7 (2020): 395–417.

[391] J. Yang, Z. Wu, N. Renier, et al., “Pathological Axonal Death Through a MAPK Cascade That Triggers a Local Energy Deficit,” Cell 160, no. 1–2 (2015): 161–176.

[392] H. B. Park and K. H. Baek, “E3 Ligases and Deubiquitinating Enzymes Regulating the MAPK Signaling Pathway in Cancers,” Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1877, no. 3 (2022): 188736.

[393] M. Amit, H. Takahashi, M. P. Dragomir, et al., “Loss of p53 Drives Neuron Reprogramming in Head and Neck Cancer,” Nature 578, no. 7795 (2020): 449–454.

[394] S. H. Manjili, M. Isbell, N. Ghochaghi, T. Perkinson, and M. H. Manjili, “Multifaceted Functions of Chronic Inflammation in Regulating Tumor Dormancy and Relapse,” Seminars in Cancer Biology 78 (2022): 17–22.

[395] H. J. Lee, J. E. Suk, C. Patrick, et al., “Direct Transfer of α-Synuclein From Neuron to Astroglia Causes Inflammatory Responses in Synucleinopathies,” Journal of Biological Chemistry 285, no. 12 (2010): 9262–9272.

[396] S. Parker, C. McDowall, L. Sanchez-Perez, et al., “Immunotoxin-αCD40 Therapy Activates Innate and Adaptive Immunity and Generates a Durable Antitumor Response in Glioblastoma Models,” Science Translational Medicine 15, no. 682 (2023): eabn5649.

[397] R. Takahashi, H. Ijichi, and M. Fujishiro, “The Role of Neural Signaling in the Pancreatic Cancer Microenvironment,” Cancers 14, no. 17 (2022): 4269.

[398] Z. Dubeykovskaya, Y. Si, X. Chen, et al., “Neural Innervation Stimulates Splenic TFF2 to Arrest Myeloid Cell Expansion and Cancer,” Nature Communications 7 (2016): 10517.

[399] Q. Zheng, H. Liu, Y. Gao, G. Cao, Y. Wang, and Z. Li, “Ameliorating Mitochondrial Dysfunction for the Therapy of Parkinson's Disease,” Small 20, no. 29 (2024): e2311571.

[400] N. Huang, S. Li, Y. Xie, Q. Han, X. M. Xu, and Z. H. Sheng, “Reprogramming an Energetic AKT-PAK5 Axis Boosts Axon Energy Supply and Facilitates Neuron Survival and Regeneration After Injury and Ischemia,” Current Biology 31, no. 14 (2021): 3098–3114 e7.

[401] P. S. Ward and C. B. Thompson, “Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate,” Cancer Cell 21, no. 3 (2012): 297–308.

[402] I. Peris, S. Romero-Murillo, E. Martínez-Balsalobre, et al., “Activation of the PP2A-B56α Heterocomplex Synergizes With Venetoclax Therapies in AML Through BCL2 and MCL1 Modulation,” Blood 141, no. 9 (2023): 1047–1059.

[403] H. C. Yoo, S. J. Park, M. Nam, et al., “A Variant of SLC1A5 Is a Mitochondrial Glutamine Transporter for Metabolic Reprogramming in Cancer Cells,” Cell Metabolism 31, no. 2 (2020): 267–283 e12.

[404] P. K. Parida, M. Marquez-Palencia, S. Ghosh, et al., “Limiting Mitochondrial Plasticity by Targeting DRP1 Induces Metabolic Reprogramming and Reduces Breast Cancer Brain Metastases,” Nature Cancer 4, no. 6 (2023): 893–907.

[405] Y. Shi, Y. Wang, H. Jiang, et al., “Mitochondrial Dysfunction Induces Radioresistance in Colorectal Cancer by Activating [Ca(2+)](m)-PDP1-PDH-Histone Acetylation Retrograde Signaling,” Cell Death & Disease 12, no. 9 (2021): 837.

[406] Z. Lei, H. Meng, L. Liu, et al., “Mitochondrial Base Editor Induces Substantial Nuclear Off-Target Mutations,” Nature 606, no. 7915 (2022): 804–811.

[407] B. N. Lizama and C. T. Chu, “Neuronal Autophagy and Mitophagy in Parkinson's Disease,” Molecular Aspects of Medicine 82 (2021): 100972.

[408] X. Li, S. He, and B. Ma, “Autophagy and Autophagy-Related Proteins in Cancer,” Molecular Cancer 19, no. 1 (2020): 12.

[409] D. P. Panigrahi, P. P. Praharaj, C. S. Bhol, et al., “The Emerging, Multifaceted Role of Mitophagy in Cancer and Cancer Therapeutics,” Seminars in Cancer Biology 66 (2020): 45–58.

[410] D. C. Wallace, “Mitochondria and Cancer,” Nature Reviews Cancer 12, no. 10 (2012): 685–698.

[411] G. Kroemer and J. Pouyssegur, “Tumor Cell Metabolism: Cancer's Achilles' Heel,” Cancer Cell 13, no. 6 (2008): 472–482.

[412] A. Takamura, M. Komatsu, T. Hara, et al., “Autophagy-Deficient Mice Develop Multiple Liver Tumors,” Genes & Development 25, no. 8 (2011): 795–800.

[413] M. Aventaggiato, E. Vernucci, F. Barreca, M. A. Russo, and M. Tafani, “Sirtuins’ Control of Autophagy and Mitophagy in Cancer,” Pharmacology & Therapeutics 221 (2021): 107748.

[414] N. Meyer, S. Zielke, J. B. Michaelis, et al., “At 101 Induces Early Mitochondrial Dysfunction and HMOX1 (Heme Oxygenase 1) to Trigger Mitophagic Cell Death in Glioma Cells,” Autophagy 14, no. 10 (2018): 1693–1709.

[415] D. Lv, R. C. Gimple, C. Zhong, et al., “PDGF Signaling Inhibits Mitophagy in Glioblastoma Stem Cells Through N-Methyladenosine,” Developmental Cell 57, no. 12 (2022): 1466–1481 e6.

[416] T. Huang, T. Xu, Y. Wang, et al., “Cannabidiol Inhibits Human Glioma by Induction of Lethal Mitophagy Through Activating TRPV4,” Autophagy 17, no. 11 (2021): 3592–3606.

[417] K. Fifel and A. Videnovic, “Chronotherapies for Parkinson's Disease,” Progress in Neurobiology 174 (2019): 16–27.

[418] K. Fifel and A. Videnovic, “Light Therapy in Parkinson's Disease: Towards Mechanism-Based Protocols,” Trends in Neurosciences 41, no. 5 (2018): 252–254.

[419] W. Ruan, X. Yuan, and H. K. Eltzschig, “Circadian Rhythm as a Therapeutic Target,” Nature Reviews Drug Discovery 20, no. 4 (2021): 287–307.

[420] A. Sancar and R. N. Van Gelder, “Clocks, Cancer, and Chronochemotherapy,” Science 371, no. 6524 (2021): eabb0738.

[421] Z. Diamantopoulou, A. Gvozdenovic, and N. Aceto, “A New Time Dimension in the Fight Against Metastasis,” Trends in Cell Biology 33, no. 9 (2023): 736–748.

[422] B. Jung-Hynes, R. J. Reiter, and N. Ahmad, “Sirtuins, Melatonin and Circadian Rhythms: Building a Bridge Between Aging and Cancer,” Journal of Pineal Research 48, no. 1 (2010): 9–19.

[423] D. D. Shi, J. A. Guo, H. I. Hoffman, et al., “Therapeutic Avenues for Cancer Neuroscience: Translational Frontiers and Clinical Opportunities,” Lancet Oncology 23, no. 2 (2022): e62–e74.

[424] H. E. Park, S. H. Jo, R. H. Lee, et al., “Spatial Transcriptomics: Technical Aspects of Recent Developments and Their Applications in Neuroscience and Cancer Research,” Advanced Science 10, no. 16 (2023): e2206939.

[425] J. C. Borniger, “Cancer Neuroscience at the Brain-Body Interface,” Genes & Development 38, no. 17–20 (2024): 787–792.

[426] S. K. Tetzlaff, E. Reyhan, N. Layer, et al., “Characterizing and Targeting Glioblastoma Neuron-Tumor Networks With Retrograde Tracing,” Cell 188, no. 2 (2025): 390–411.e36.

[427] D. Sturm, D. Capper, F. Andreiuolo, et al., “Multiomic Neuropathology Improves Diagnostic Accuracy in Pediatric Neuro-Oncology,” Nature Medicine 29, no. 4 (2023): 917–926.

[428] V. Wischnewski, R. R. Maas, P. G. Aruffo, et al., “Phenotypic Diversity of T Cells in Human Primary and Metastatic Brain Tumors Revealed by Multiomic Interrogation,” Nature Cancer 4, no. 6 (2023): 908–924.

[429] F. Danzi, R. Pacchiana, A. Mafficini, et al., “To Metabolomics and Beyond: A Technological Portfolio to Investigate Cancer Metabolism,” Signal Transduction and Targeted Therapy 8, no. 1 (2023): 137.

[430] D. Rosenblum, A. Gutkin, R. Kedmi, et al., “CRISPR-Cas9 Genome Editing Using Targeted Lipid Nanoparticles for Cancer Therapy,” Science Advances 6, no. 47 (2020): abc9450.

[431] S. W. Wang, C. Gao, Y. M. Zheng, et al., “Current Applications and Future Perspective of CRISPR/Cas9 Gene Editing in Cancer,” Molecular Cancer 21, no. 1 (2022): 57.

[432] M. Tyumentseva, A. Tyumentsev, and V. Akimkin, “CRISPR/Cas9 Landscape: Current State and Future Perspectives,” International Journal of Molecular Sciences 24, no. 22 (2023): 16077.

[433] E. Li, C. Benitez, S. C. Boggess, et al., “Crispri-Based Screens in Iassembloids to Elucidate Neuron-Glia Interactions,” Neuron 113, no. 5 (2025): 701–718.e8.

[434] L. Bendixen, T. I. Jensen, and R. O. Bak, “CRISPR-Cas-Mediated Transcriptional Modulation: The Therapeutic Promises of CRISPRa and CRISPRi,” Molecular Therapy 31, no. 7 (2023): 1920–1937.

[435] S. Maharjan, C. Ma, B. Singh, et al., “Advanced 3D Imaging and Organoid Bioprinting for Biomedical Research and Therapeutic Applications,” Advanced Drug Delivery Reviews 208 (2024): 115237.

[436] A. C. Juraski, S. Sharma, S. Sparanese, et al., “3D Bioprinting for Organ and Organoid Models and Disease Modeling,” Expert Opinion on Drug Discovery 18, no. 9 (2023): 1043–1059.

[437] J. Oppermann, A. Rozenberg, T. Fabrin, et al., “Robust Optogenetic Inhibition With Red-Light-Sensitive Anion-Conducting Channelrhodopsins,” eLife 12 (2024): e90100.

[438] R. Selote and R. Makhijani, “A Knowledge Graph Approach to Drug Repurposing for Alzheimer's, Parkinson's and Glioma Using Drug-Disease-Gene Associations,” Computational Biology and Chemistry 115 (2025): 108302.

[439] V. Jain, H. Kumar, H. V. Anod, et al., “A Review of Nanotechnology-Based Approaches for Breast Cancer and Triple-Negative Breast Cancer,” Journal of Controlled Release 326 (2020): 628–647.

[440] L. Yang, A. Li, Y. Wang, and Y. Zhang, “Intratumoral Microbiota: Roles in Cancer Initiation, Development and Therapeutic Efficacy,” Signal Transduction and Targeted Therapy 8, no. 1 (2023): 35.

[441] B. Högl, “Circadian Rhythms and Chronotherapeutics-Underappreciated Approach to Improving Sleep and Wakefulness in Parkinson Disease,” JAMA Neurology 74, no. 4 (2017): 387–388.

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