Advances in Gene Therapy for Neurologic Disorders: An Overview

Pallavi Chand , K. Trideva Sastri , Ashish Singh Chauhan , Souvik Chakraborty , Vikash Jakhmola

BIO Integration ›› 2025, Vol. 6 ›› Issue (1) : 4

PDF (1682KB)
BIO Integration ›› 2025, Vol. 6 ›› Issue (1) :4 DOI: 10.15212/bioi-2024-0060
Mini Review
research-article
Advances in Gene Therapy for Neurologic Disorders: An Overview
Author information +
History +
PDF (1682KB)

Abstract

Neurologic disorders currently affect approximately 100 million people worldwide. Neurologic disorders most often occur due to inherent genetic mutations, which lead to numerous types of functional disruptions in nervous system development. Neurologic disease-related events, such as genetic and epigenetic changes, cause inflammatory processes in the area which may enhance the disease cycle. Gene therapy has progressed to a compelling therapeutic approach for various neurodegenerative disorders. Several efforts to enhance gene therapy rely on discovering novel vectors, recent curative targets, and the dependability of transgenic delivery paths. These viral and non-viral vectors techniques are carefully screened through preclinical and clinical levels and eventually render patients with effective therapies. This review addresses gene therapy developments and obstacles for neurodegenerative diseases and discusses emerging strategies, goals, and prospects.

Keywords

Adeno-associated viruses / gene therapy / lipid-based vectors / neurologic disorders / non-viral and viral vectors

Cite this article

Download citation ▾
Pallavi Chand, K. Trideva Sastri, Ashish Singh Chauhan, Souvik Chakraborty, Vikash Jakhmola. Advances in Gene Therapy for Neurologic Disorders: An Overview. BIO Integration, 2025, 6 (1) : 4 DOI:10.15212/bioi-2024-0060

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Dunbar CE, High KA, Joung JK, Kohn DB, Ozawa K, et al. Gene therapy comes of age. Science 2018; 359(6372): eaan4672. [PMID: 29326244 DOI: 10.1126/SCIENCE.AAN4672]

[2]

Hudry E, Vandenberghe LH. Therapeutic AAV gene transfer to the nervous system: a clinical reality. Neuron 2019; 102(1): 263. [PMID: 30946822 DOI: 10.1016/j.neuron.2019.03.020]

[3]

Wang D, Tai PWL, Gao G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat Rev Drug Discov 2019; 18(5): 358-78. [PMID: 30710128 DOI: 10.1038/s41573-019-0012-9]

[4]

Lee JH, Wang JH, Chen J, Li F, Edwards TL, et al. Gene therapy for visual loss: opportunities and concerns. Prog Retin Eye Res 2019; 68: 31-53. [PMID: 30170104 DOI: 10.1016/j.preteyeres.2018.08.003]

[5]

Samaranch L, Salegio EA, San Sebastian W, Kells AP, Bringas JR, et al. Strong cortical and spinal cord transduction after AAV7 and AAV9 delivery into the cerebrospinal fluid of nonhuman primates. Hum Gene Ther 2013; 24(5): 526-32. [PMID: 23517473 DOI: 10.1089/hum.2013.005]

[6]

Xiang C, Zhang Y, Guo W, Liang XJ. Biomimetic carbon nanotubes for neurological disease therapeutics as inherent medication. Acta Pharm Sin B 2020; 10(2): 239-48. [PMID: 32082970 DOI: 10.1016/j.apsb.2019.11.003]

[7]

Cearley CN, Vandenberghe LH, Parente MK, Carnish ER, Wilson JM, et al. Expanded repertoire of AAV vector serotypes mediate unique patterns of transduction in mouse brain. Mol Ther 2008; 16(10): 1710-8. [PMID: 18714307 DOI: 10.1038/mt.2008.166]

[8]

Bartlett JS, Samulski RJ, McCown TJ. Selective and rapid uptake of adeno-associated virus type 2 in brain. Hum Gene Ther 1998; 9(8): 1181-6. [PMID: 9625257 DOI: 10.1089/hum.1998.9.8-1181]

[9]

Hutson TH, Verhaagen J, Yáñez-Muñoz RJ, Moon LDF. Corticospinal tract transduction: a comparison of seven adeno-associated viral vector serotypes and a non-integrating lentiviral vector. Gene Ther 2012; 19(1): 49-60. [PMID: 21562590 DOI: 10.1038/gt.2011.71]

[10]

Katz ML, Tecedor L, Chen Y, Williamson BG, Lysenko E, et al. AAV gene transfer delays disease onset in a TPP1-deficient canine model of the late infantile form of Batten disease. Sci Transl Med 2015; 7(313): 313ra180. [PMID: 26560358 DOI: 10.1126/scitranslmed.aac6191]

[11]

Federici T, Taub JS, Baum GR, Gray SJ, Grieger JC, et al. Robust spinal motor neuron transduction following intrathecal delivery of AAV9 in pigs. Gene Ther 2012; 19(8): 852-9. [PMID: 21918551 DOI: 10.1038/gt.2011.130]

[12]

Passini MA, Watson DJ, Vite CH, Landsburg DJ, Feigenbaum AL, et al. Intraventricular brain injection of adeno-associated virus type 1 (AAV1) in neonatal mice results in complementary patterns of neuronal transduction to AAV2 and total long-term correction of storage lesions in the brains of beta-glucuronidase-deficient mice. J Virol 2003; 77(12): 7034-40. [PMID: 12768022 DOI: 10.1128/jvi.77.12.7034-7040.2003]

[13]

Marks WJ, Ostrem JL, Verhagen L, Starr PA, Larson PS, et al. Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2-neurturin) to patients with idiopathic Parkinson’s disease: an open-label, phase I trial. Lancet Neurol 2008; 7(5): 400-8. [PMID: 18387850 DOI: 10.1016/S1474-4422(08)70065-6]

[14]

Rafii MS, Tuszynski MH, Thomas RG, Barba D, Brewer JB, et al. Adeno-associated viral vector (serotype 2)-nerve growth factor for patients with Alzheimer disease: a randomized clinical trial. JAMA Neurol 2018; 75(7): 834-41. [PMID: 29582053 DOI: 10.1001/jamaneurol.2018.0233]

[15]

Adachi K, Enoki T, Kawano Y, Veraz M, Nakai H. Drawing a high-resolution functional map of adeno-associated virus capsid by massively parallel sequencing. Nat Commun 2014; 5: 3075. [PMID: 24435020 DOI: 10.1038/ncomms4075]

[16]

Albright BH, Storey CM, Murlidharan G, Castellanos Rivera RM, Berry GE, et al. Mapping the structural determinants required for AAVrh.10 transport across the blood-brain barrier. Mol Ther 2018; 26(2): 510-23. [PMID: 29175157 DOI: 10.1016/j.ymthe.2017.10.017]

[17]

Allen WE, Kauvar IV, Chen MZ, Richman EB, Yang SJ, et al. Global representations of goal-directed behavior in distinct cell types of mouse neocortex. Neuron 2017; 94(4): 891-907.e6. [PMID: 28521139 DOI: 10.1016/j.neuron.2017.04.017]

[18]

Dalkara D, Byrne LC, Klimczak RR, Visel M, Yin L, et al. In vivo-directed evolution of a new adeno-associated virus for therapeutic outer retinal gene delivery from the vitreous. Sci Transl Med 2013; 5(189): 189ra76. [PMID: 23761039 DOI: 10.1126/scitranslmed.3005708]

[19]

Barkats M, Bilang-Bleuel A, Buc-Caron MH, Castel-Barthe MN, Corti O, et al. Adenovirus in the brain: recent advances of gene therapy for neurodegenerative diseases. Prog Neurobiol 1998; 55(4): 333-41. [PMID: 9654383 DOI: 10.1016/s0301-0082(98)00028-8]

[20]

Kritzinger A, Ferger B, Gillardon F, Stierstorfer B, Birk G, et al. Age-related pathology after adenoviral overexpression of the leucine-rich repeat kinase 2 in the mouse striatum. Neurobiol Aging 2018; 66: 97-111. [PMID: 29550548 DOI: 10.1016/j.neurobiolaging.2018.02.008]

[21]

Pack DW, Hoffman AS, Pun S, Stayton PS. Design and development of polymers for gene delivery. Nat Rev Drug Discov 2005; 4(7): 581-93. [PMID: 16052241 DOI: 10.1038/nrd1775]

[22]

Mintzer MA, Simanek EE. Nonviral vectors for gene delivery. Chem Rev 2009; 109(2): 259-302. [PMID: 19053809 DOI: 10.1021/cr800409e]

[23]

Buck J, Grossen P, Cullis PR, Huwyler J, Witzigmann D . Lipid-based DNA therapeutics: hallmarks of non-viral gene delivery. ACS Nano 2019; 13(4): 3754-82. [PMID: 30908008 DOI: 10.1021/acsnano.8b07858]

[24]

Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, et al. Non-viral vectors for gene-based therapy. Nat Rev Genet 2014; 15(8): 541-55. [PMID: 25022906 DOI: 10.1038/nrg3763]

[25]

Li W, Szoka FC. Lipid-based nanoparticles for nucleic acid delivery. Pharm Res 2007; 24(3): 438-49. [PMID: 17252188 DOI: 10.1007/s11095-006-9180-5]

[26]

Conceição M, Mendonça L, Nóbrega C, Gomes C, Costa P, et al. Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Machado-Joseph disease neurological phenotype. Biomaterials 2016; 82: 124-37. [PMID: 26757259 DOI: 10.1016/j.biomaterials.2015.12.021]

[27]

Carradori D, Eyer J, Saulnier P, Préat V, des Rieux A. The therapeutic contribution of nanomedicine to treat neurodegenerative diseases via neural stem cell differentiation. Biomaterials 2017; 123: 77-91. [PMID: 28161683 DOI: 10.1016/j.biomaterials.2017.01.032]

[28]

Niu S, Zhang LK, Zhang L, Zhuang S, Zhan X, et al. Inhibition by multifunctional magnetic nanoparticles loaded with alpha-synuclein RNAi plasmid in a Parkinson’s disease model. Theranostics 2017; 7(2): 344-56. [PMID: 28042339 DOI: 10.7150/thno.16562]

[29]

Semple SC, Akin A, Chen J, Sandhu AP, Mui BL, et al. Rational design of cationic lipids for siRNA delivery. Nat Biotechnol 2010; 28(2): 172-6. [PMID: 20081866 DOI: 10.1038/nbt.1602]

[30]

Kojima R, Bojar D, Rizzi G, Hamri GC, El-Baba MD, et al. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment. Nat Commun 2018; 9(1): 1305. [PMID: 29610454 DOI: 10.1038/s41467-018-03733-8]

[31]

Chen W, Luan J, Wei G, Zhang X, Fan J, et al. In vivo hepatocellular expression of interleukin-22 using penetratin-based hybrid nanoparticles as potential anti-hepatitis therapeutics. Biomaterials 2018; 187: 66-80. [PMID: 30296739 DOI: 10.1016/j.biomaterials.2018.09.046]

[32]

Morris VB, Labhasetwar V. Arginine-rich polyplexes for gene delivery to neuronal cells. Biomaterials 2015; 60: 151- 60. [PMID: 26000961 DOI: 10.1016/j.biomaterials.2015.04.052]

[33]

Malhotra M, Tomaro-Duchesneau C, Prakash S. Synthesis of TAT peptide-tagged PEGylated chitosan nanoparticles for siRNA delivery targeting neurodegenerative diseases. Biomaterials 2013; 34(4): 1270-80. [PMID: 23140978 DOI: 10.1016/j.biomaterials.2012.10.013]

[34]

Hitti FL, Gonzalez-Alegre P, Lucas TH. Gene therapy for neurologic disease: a neurosurgical review. World Neurosurg 2019; 121: 261-73. [PMID: 30253990 DOI: 10.1016/j.wneu.2018.09.097]

[35]

Cree BAC. Multiple sclerosis genetics. Mult Scler Relat Disord 2018. [DOI: 10.1891/9780826125941.0005]

[36]

Correale J, Gaitán MI, Ysrraelit MC, Fiol MP. Progressive multiple sclerosis: from pathogenic mechanisms to treatment. Brain 2017; 140(3): 527-46. [PMID: 27794524 DOI: 10.1093/brain/aww258]

[37]

Capone A, Bianco M, Ruocco G, de Bardi M, Battistini L, et al. Distinct expression of inflammatory features in T helper 17 cells from multiple sclerosis patients. Cells 2019; 8: 533. [PMID: 31167379 DOI: 10.3390/cells8060533]

[38]

Li QW, Lei W, Chen C, Guo W. Recent advances of long noncoding RNAs involved in the development of multiple sclerosis. Chin J Nat Med 2020; 18(1): 36-46. [PMID: 31955822 DOI: 10.1016/S1875-5364(20)30003-0]

[39]

Piket E, Zheleznyakova GY, Kular L, Jagodic M. Small non-coding RNAs as important players, biomarkers and therapeutic targets in multiple sclerosis: a comprehensive overview. J Autoimmun 2019; 101: 17-25. [PMID: 31014917 DOI: 10.1016/j.jaut.2019.04.002]

[40]

Fenoglio C, Cantoni C, De Riz M, Ridolfi E, Cortini F, et al. Expression and genetic analysis of miRNAs involved in CD4+ cell activation in patients with multiple sclerosis. Neurosci Lett 2011; 504(1): 9-12. [PMID: 21875645 DOI: 10.1016/j.neulet.2011.08.021]

[41]

Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 2017; 16(3): 203-22. [PMID: 28209991 DOI: 10.1038/nrd.2016.246]

[42]

Mohamed MS, Nahrery EMAE, Shalaby N, Hussein M, Aal RAE, et al. Micro-RNA 18b and interleukin 17A profiles in relapsing remitting multiple sclerosis. Mult Scler Relat Disord 2019; 28: 226-9. [PMID: 30623862 DOI: 10.1016/j.msard.2018.12.013]

[43]

Zhang F, Liu G, Wei C, Gao C, Hao J. Linc-MAF-4 regulates Th1/Th2 differentiation and is associated with the pathogenesis of multiple sclerosis by targeting MAF. FASEB J 2017; 31(2): 519-25. [PMID: 27756768 DOI: 10.1096/fj.201600838R]

[44]

Ranzani V, Rossetti G, Panzeri I, Arrigoni A, Bonnal RJ, et al. The long intergenic noncoding RNA landscape of human lymphocytes highlights the regulation of T cell differentiation by linc-MAF-4. Nat Immunol 2015; 16(3): 318-25. [PMID: 25621826 DOI: 10.1038/ni.3093]

[45]

Portoso M, Ragazzini R, Brenčič Ž, Moiani A, Michaud A, et al. PRC2 is dispensable for HOTAIR-mediated transcriptional repression. EMBO J 2017; 36(8): 981-94. [PMID: 28167697 DOI: 10.15252/embj.201695335]

[46]

Song J, Kim D, Han J, Kim Y, Lee M, et al. PBMC and exosome-derived Hotair is a critical regulator and potent marker for rheumatoid arthritis. Clin Exp Med 2015; 15: 121-6. [PMID: 24722995 DOI: 10.1007/s10238-013-0271-4]

[47]

Li Z, Li X, Jiang C, Qian W, Tse G, et al. Long non-coding RNAs in rheumatoid arthritis. Cell Prolif 2018; 51: e12404. [PMID: 29110355 DOI: 10.1111/cpr.12404]

[48]

Pahlevan Kakhki M, Nikravesh A, Shirvani Farsani Z, Sahraian MA, Behmanesh M. HOTAIR but not ANRIL long non-coding RNA contributes to the pathogenesis of multiple sclerosis. Immunology 2018; 153: 479-87. [PMID: 29030863 DOI: 10.1111/imm.12850]

[49]

Sun S, Wu Y, Guo W, Yu F, Kong L, et al. STAT3/HOTAIR signaling axis regulates HNSCC growth in an EZH2-dependent manner. Clin Cancer Res 2018; 24: 2665-77. [PMID: 29540490 DOI: 10.1158/1078-0432.CCR-16-2248]

[50]

Guo W, Luo C, Wang C, Zhu Y, Wang X, et al. Protection against Th17 cells differentiation by an interleukin-23 receptor cytokine-binding homology region. PLoS One 2012; 7: e45625. [PMID: 23029144 DOI: 10.1371/journal.pone.0045625]

[51]

Guo W, Luo C, Wang C, Wang YH, Wang X, et al. Suppression of human and mouse Th17 differentiation and autoimmunity by an endogenous Interleukin 23 receptor cytokine-binding homology region. Int J Biochem Cell Biol 2014; 55: 304-10. [PMID: 25263529 DOI: 10.1016/j.biocel.2014.09.019]

[52]

Guo W, Lei W, Yu D, Ge Y, Chen Y, et al. Involvement of lncRNA-1700040D17Rik in Th17 cell differentiation and the pathogenesis of EAE. Int Immunopharmacol 2017; 47: 141-9. [PMID: 28395256 DOI: 10.1016/j.intimp.2017.03.014]

[53]

Aylward EH, Codori AM, Rosenblatt A, Sherr M, Brandt J, et al. Rate of caudate atrophy in presymptomatic and symptomatic stages of Huntington’s disease. Mov Disord 2000; 15: 552-60. [PMID: 10830423 DOI: 10.1002/1531-8257(200005)15:3[[552::AID-MDS1020]]3.0.CO;2-P]

[54]

MacDonald ME, Ambrose CM, Duyao MP, Myers RH, Lin C, et al. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 1993; 72: 971-83. [DOI: 10.1016/0092-8674(93)90585-E]

[55]

Rawlins MD, Wexler NS, Wexler AR, Tabrizi SJ, Douglas I, et al. The prevalence of Huntington’s disease. Neuroepidemiology 2016; 46: 144-53. [PMID: 26824438 DOI: 10.1159/000443738]

[56]

Roos RAC. Huntington’s disease: a clinical review. Orphanet J Rare Dis 2010; 5: 40. [PMID: 21171977 DOI: 10.1186/1750-1172-5-40]

[57]

Landles C, Bates GP. Huntingtin and the molecular pathogenesis of Huntington’s disease. EMBO Rep 2004; 5: 958-63. [PMID: 15459747 DOI: 10.1038/sj.embor.7400250]

[58]

Wild EJ, Boggio R, Langbehn D, Robertson N, Haider S, et al. Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington’s disease patients. J Clin Invest 2015; 125: 1979-86. [PMID: 25844897 DOI: 10.1172/JCI80743]

[59]

Sava V, Fihurka O, Khvorova A, Sanchez-Ramos J. Enriched chitosan nanoparticles loaded with siRNA are effective in lowering Huntington’s disease gene expression following intranasal administration. Nanomedicine 2020; 24: 102119. [PMID: 31666200 DOI: 10.1016/j.nano.2019.102119]

[60]

Kacher R, Lamazière A, Heck N, Kappes V, Mounier C, et al. CYP46A1 gene therapy deciphers the role of brain cholesterol metabolism in Huntington’s disease. Brain 2019; 142: 2432-50. [PMID: 31286142 DOI: 10.1093/brain/awz174]

[61]

Spronck EA, Brouwers CC, Vallès A, de Haan M, Petry H, et al. AAV5-miHTT gene therapy demonstrates sustained Huntingtin lowering and functional improvement in Huntington disease mouse models. Mol Ther Methods Clin Dev 2019; 13: 334-43. [PMID: 30984798 DOI: 10.1016/j.omtm.2019.03.002]

[62]

Zeitler B, Froelich S, Marlen K, Shivak DA, Yu Q, et al. Allele-selective transcriptional repression of mutant HTT for the treatment of Huntington’s disease. Nat Med 2019; 25: 1131-42. [PMID: 31263285 DOI: 10.1038/s41591-019-0478-3]

[63]

Verma MK, Goel R, Nandakumar K, Nemmani KVS. Bilateral quinolinic acid-induced lipid peroxidation, decreased striatal monoamine levels and neurobehavioral deficits are ameliorated by GIP receptor agonist D-Ala2GIP in rat model of Huntington’s disease. Eur J Pharmacol 2018; 828: 31-41. [PMID: 29577894 DOI: 10.1016/j.ejphar.2018.03.034]

[64]

Pfister EL, Dinardo N, Mondo E, Borel F, Conroy F, et al. Artificial miRNAs reduce human mutant Huntingtin throughout the striatum in a transgenic sheep model of Huntington’s disease. Hum Gene Ther 2018; 29: 663-73. [PMID: 29207890 DOI: 10.1089/hum.2017.199]

[65]

Yang S, Li S, Li X, Yang S, Chang R, et al. CRISPR/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington’s disease. J Clin Invest 2017; 127: 2719-24. [PMID: 28628038 DOI: 10.1172/JCI92087]

[66]

Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol 2010; 22: 124-31. [PMID: 20034776 DOI: 10.1016/j.ceb.2009.11.014]

[67]

Freude K, Krauss S. Dementia, brain disorders and molecular mechanisms. J Mol Biol 2019; 431: 1709-10. [PMID: 30930050 DOI: 10.1016/j.jmb.2019.03.025]

[68]

Winblad B, Amouyel P, Andrieu S, Ballard C, Brayne C, et al. Defeating Alzheimer’s disease and other dementias: a priority for European science and society. Lancet Neurol 2016; 15: 455-532. [PMID: 26987701 DOI: 10.1016/S1474-4422(16)00062-4]

[69]

Rodriguez-Vieitez E, Saint-Aubert L, Carter SF, Almkvist O, Farid K, et al. Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer’s disease. Brain 2016; 139: 922-36. [PMID: 26813969 DOI: 10.1093/brain/awv404]

[70]

Nixon RA. Autophagy, amyloidogenesis and Alzheimer disease. J Cell Sci 2007; 120: 4081-91. [PMID: 18032783 DOI: 10.1242/jcs.019265]

[71]

Hong CS, Goins WF, Goss JR, Burton EA, Glorioso JC. Herpes simplex virus RNAi and neprilysin gene transfer vectors reduce accumulation of Alzheimer’s disease-related amyloid-β peptide in vivo. Gene Ther 2006; 13: 1068-79. [PMID: 16541122 DOI: 10.1038/sj.gt.3302719]

[72]

Senechal Y, Kelly PH, Cryan JF, Natt F, Dev KK. Amyloid precursor protein knockdown by siRNA impairs spontaneous alternation in adult mice. J Neurochem 2007; 102: 1928-40. [PMID: 17540010 DOI: 10.1111/j.1471-4159.2007.04672.x]

[73]

Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 2011; 29: 341-5. [PMID: 21423189 DOI: 10.1038/nbt.1807]

[74]

Singer O, Marr RA, Rockenstein E, Crews L, Coufal NG, et al. Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model. Nat Neurosci 2005; 8: 1343-9. [PMID: 16136043 DOI: 10.1038/nn1531]

[75]

Hu X, Zhou X, He W, Yang J, Xiong W, et al. BACE1 deficiency causes altered neuronal activity and neurodegeneration. J Neurosci 2010; 30: 8819-29. [PMID: 20592204 DOI: 10.1523/JNEUROSCI.1334-10.2010]

[76]

Fitz NF, Cronican AA, Saleem M, Fauq AH, Chapman R, et al. Abca1 deficiency affects Alzheimer’s disease-like phenotype in human ApoE4 but not in ApoE3-targeted replacement mice. J Neurosci 2012; 32: 13125-36. [PMID: 22993429 DOI: 10.1523/JNEUROSCI.1937-12.2012]

[77]

Donkin JJ, Stukas S, Hirsch-Reinshagen V, Namjoshi D, Wilkinson A, et al. ATP-binding cassette transporter A1 mediates the beneficial effects of the liver X receptor agonist GW3965 on object recognition memory and amyloid burden in amyloid precursor protein/presenilin 1 mice. J Biol Chem 2010; 285: 34144-54. [PMID: 20739291 DOI: 10.1074/jbc.M110.108100]

[78]

Zelcer N, Khanlou N, Clare R, Jiang Q, Reed-Geaghan EG, et al. Attenuation of neuroinflammation and Alzheimer’s disease pathology by liver x receptors. Proc Natl Acad Sci U S A 2007; 104: 10601-6. [PMID: 17563384 DOI: 10.1073/pnas.0701096104]

[79]

Egan CM, Nyman U, Skotte J, Streubel G, Turner S, et al. CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression. Dev Cell 2013; 26: 223-36. [PMID: 23948251 DOI: 10.1016/j.devcel.2013.07.008]

[80]

Sánchez-Pulido L, Devos D, Valencia A. BRICHOS: a conserved domain in proteins associated with dementia, respiratory distress and cancer. Trends Biochem Sci 2002; 27: 329-32. [PMID: 12114016 DOI: 10.1016/s0968-0004(02)02134-5]

[81]

Willander H, Askarieh G, Landreh M, Westermark P, Nordling K, et al. High-resolution structure of a BRICHOS domain and its implications for anti-amyloid chaperone activity on lung surfactant protein C. Proc Natl Acad Sci U S A 2012; 109: 2325-9. [PMID: 22308375 DOI: 10.1073/pnas.1114740109]

[82]

Willander H, Hermansson E, Johansson J, Presto J. BRICHOS domain associated with lung fibrosis, dementia and cancer - a chaperone that prevents amyloid fibril formation? FEBS J 2011; 278: 3893-904. [PMID: 21668643 DOI: 10.1111/j.1742-4658.2011.08209.x]

[83]

Hermansson E, Schultz S, Crowther D, Linse S, Winblad B, et al. The chaperone domain BRICHOS prevents CNS toxicity of amyloid-β peptide in Drosophila melanogaster. Dis Model Mech 2014; 7: 659-65. [PMID: 24682783 DOI: 10.1242/dmm.014787]

[84]

Arosio P, Michaels T, Linse S, Månsson C, Emanuelsson C, et al. Kinetic analysis reveals the diversity of microscopic mechanisms through which molecular chaperones suppress amyloid formation. Nat Commun 2016; 7: 10948. [PMID: 27009901 DOI: 10.1038/ncomms10948]

[85]

Kim J, Chakrabarty P, Hanna A, March A, Dickson DW, et al. Normal cognition in transgenic BRI2-Aβ mice. Mol Neurodegener 2013; 8: 15. [PMID: 23663320 DOI: 10.1186/1750-1326-8-15]

[86]

Cohen SIA, Arosio P, Presto J, Kurudenkandy FR, Biverstål H, et al. A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers. Nat Struct Mol Biol 2015; 22: 207-13. [PMID: 25686087 DOI: 10.1038/nsmb.2971]

[87]

Poska H, Haslbeck M, Kurudenkandy FR, Hermansson E, Chen G, et al. Dementia-related Bri2 BRICHOS is a versatile molecular chaperone that efficiently inhibits Aβ42 toxicity in Drosophila. Biochem J 2016; 473: 3683-704. [PMID: 27514716 DOI: 10.1042/BCJ20160277]

[88]

Menzies FM, Fleming A, Rubinsztein DC. Compromised autophagy and neurodegenerative diseases. Nat Rev Neurosci 2015; 16: 345-57. [PMID: 25991442 DOI: 10.1038/nrn3961]

[89]

Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, et al. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 2007; 282: 24131-45. [PMID: 17580304 DOI: 10.1074/jbc.M702824200]

[90]

Komatsu M, Waguri S, Chiba T, Murata S, Iwata JI, et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 2006; 441: 880-4. [PMID: 16625205 DOI: 10.1038/nature04723]

[91]

Kim M, Sandford E, Gatica D, Qiu Y, Liu X, et al. Mutation in ATG5 reduces autophagy and leads to ataxia with developmental delay. Elife 2016; 5: e12245. [PMID: 26812546 DOI: 10.7554/elife.12245]

[92]

Nakamura Y, Saigoh K, Sakamoto H, Ueno S, Isono C, et al. Mutations in the gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis. Neurology 2013; 80: 458-63. [PMID: 23303844 DOI: 10.1212/WNL.0b013e31827f0fe5]

[93]

le Ber I, Camuzat A, Guerreiro R, Bouya-Ahmed K, Bras J, et al. SQSTM1 Mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis. JAMA Neurol 2013; 70: 1403-10. [PMID: 24042580 DOI: 10.1001/jamaneurol.2013.3849]

[94]

Nilsson P, Loganathan K, Sekiguchi M, Matsuba Y, Hui K, et al. Aβ secretion and plaque formation depend on autophagy. Cell Rep 2013; 5: 61-9. [PMID: 24095740 DOI: 10.1016/j.celrep.2013.08.042]

[95]

Wichmann T, DeLong MR. Pathophysiology of Parkinson’s disease: the MPTP primate model of the human disorder. Ann N Y Acad Sci 2003; 991: 199-213. [PMID: 12846988 DOI: 10.1111/j.1749-6632.2003.tb07477.x]

[96]

Alvarez L, Macias R, Guridi J, Lopez G, Alvarez E, et al. Dorsal subthalamotomy for Parkinson’s disease. Mov Disord 2001; 16: 72-8. [PMID: 11215596 DOI: 10.1002/1531-8257(200101)16:1[[72::aid-mds1019]]3.0.co;2-6]

[97]

Su PC, Tseng HM, Liu HM, Yen RF, Liou HH. Treatment of advanced Parkinson’s disease by subthalamotomy: one-year results. Mov Disord 2003; 18: 531-8. [PMID: 12722167 DOI: 10.1002/mds.10393]

[98]

Obeso JA. Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson’s disease. N Engl J Med 2019; 345: 956-63. [PMID: 11575287 DOI: 10.1056/NEJMoa000827]

[99]

Levy R, Lang AE, Dostrovsky JO, Pahapill P, Romas J, et al. Lidocaine and muscimol microinjections in subthalamic nucleus reverse Parkinsonian symptoms. Brain 2001; 124: 2105-18. [PMID: 11571226 DOI: 10.1093/brain/124.10.2105]

[100]

Jarraya B, Boulet S, Ralph GS, Jan C, Bonvento G, et al. Dopamine gene therapy for Parkinson’s disease in a nonhuman primate without associated dyskinesia. Sci Transl Med 2009; 1: 2ra4. [PMID: 20368163 DOI: 10.1126/scitranslmed.3000130]

[101]

Warrington KH, Herzog RW. Treatment of human disease by adeno-associated viral gene transfer. Hum Genet 2006; 119: 571-603. [PMID: 16612615 DOI: 10.1007/s00439-006-0165-6]

[102]

Sengupta R, Mukherjee C, Sarkar N, Sun Z, Lesnik J, et al. An optimized protocol for packaging pseudotyped Integrase defective lentivirus. Biol Proced Online 2016; 18: 14. [PMID: 27403084 DOI: 10.1186/s12575-016-0044-z]

[103]

Latchman DS. Gene delivery and gene therapy with herpes simplex virus-based vectors. Gene 2001; 264: 1-9. [PMID: 11245972 DOI: 10.1016/s0378-1119(01)00322-5]

[104]

Hocquemiller M, Giersch L, Audrain M, Parker S, Cartier N. Adeno-associated virus-based gene therapy for CNS diseases. Hum Gene Ther 2016; 27: 478-96. [PMID: 27267688 DOI: 10.1089/hum.2016.087]

[105]

Marquez Loza LI, Yuen EC, McCray PB. Lentiviral vectors for the treatment and prevention of cystic fibrosis lung disease. Genes (Basel) 2019; 10: 218. [PMID: 30875857 DOI: 10.3390/genes10030218]

[106]

Sehara Y, Fujimoto KI, Ikeguchi K, Katakai Y, Ono F, et al. Persistent expression of dopamine-synthesizing enzymes 15 years after gene transfer in a primate model of Parkinson’s disease. Hum Gene Ther Clin Dev 2017; 28: 74-9. [PMID: 28279081 DOI: 10.1089/humc.2017.010]

[107]

Nagatsua T, Sawadab M. L-Dopa therapy for Parkinson’s disease: past, present, and future. Parkinsonism Relat Disord 2009; 15: S3-8. [PMID: 19131039 DOI: 10.1016/S1353-8020(09)70004-5]

[108]

Christine CW, Starr PA, Larson PS, Eberling JL, Jagust WJ, et al. Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology 2009; 73: 1662-9. [PMID: 19828868 DOI: 10.1212/WNL.0b013e3181c29356]

[109]

Eberling JL, Jagust WJ, Christine CW, Starr P, Larson P, et al. Results from a phase I safety trial of hAADC gene therapy for Parkinson disease. Neurology 2008; 70: 1980-3. [PMID: 18401019 DOI: 10.1212/01.wnl.0000312381.29287.ff]

[110]

Muramatsu SI, Fujimoto KI, Kato S, Mizukami H, Asari S, et al. A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson’s disease. Mol Therapy 2010; 18: 1731-5. [PMID: 20606642 DOI: 10.1038/mt.2010.135]

[111]

Christine CW, Bankiewicz KS, Van Laar AD, Richardson RM, Ravina B, et al. Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson’s disease. Ann Neurol 2019; 85: 704-14. [PMID: 30802998 DOI: 10.1002/ana.25450]

[112]

Han SJ, Bankiewicz K, Butowski NA, Larson PS, Aghi MK. Interventional MRI-guided catheter placement and real time drug delivery to the central nervous system. Expert Rev Neurother 2016; 16: 635-9. [PMID: 27054877 DOI: 10.1080/14737175.2016.1175939]

[113]

Gill SS, Patel NK, Hotton GR, O’Sullivan K, McCarter R, et al. Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med 2003; 9: 589-95. [PMID: 12669033 DOI: 10.1038/nm850]

[114]

Whone A, Luz M, Boca M, Woolley M, Mooney L, et al. Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson’s disease. Brain 2019; 142: 512-25. [PMID: 30808022 DOI: 10.1093/brain/awz023]

[115]

Whone AL, Boca M, Luz M, Woolley M, Mooney L, et al. Extended treatment with glial cell line-derived neurotrophic factor in Parkinson’s disease. J Parkinsons Dis 2019; 9: 301-13. [PMID: 30829619 DOI: 10.3233/JPD-191576]

[116]

Review N, Circuits BG. Circuits and circuit disorders of the basal ganglia. Arch Neurol 2007; 64: 20-4. [PMID: 17210805 DOI: 10.1001/archneur.64.1.20]

[117]

Obeso JA, Rodriguez-Oroz MC, Rodriguez M, Macias R, Alvarez L, et al. Pathophysiologic basis of surgery for Parkinson’s disease. Neurology 2000; 55: S7-12. [PMID: 11188978]

[118]

Erlander MG, Tillakaratne NJK, Feldblum S, Patel N, Tobin AJ. Two genes encode distinct glutamate decarboxylases. Neuron 1991; 7: 91-100. [PMID: 2069816 DOI: 10.1016/0896-6273(91)90077-d]

[119]

Münster-Wandowski A, Zander J-F, Richter K, Ahnert-Hilger G . Co-existence of functionally different vesicular neurotransmitter transporters. Front Synaptic Neurosci 2016; 8: 4. [PMID: 26909036 DOI: 10.3389/fnsyn.2016.00004]

[120]

Roccaro-Waldmeyer DM, Girard F, Milani D, Vannoni E, Prétôt L, et al. Eliminating the VGlut2-dependent glutamatergic transmission of parvalbumin-expressing neurons leads to deficits in locomotion and vocalization, decreased pain sensitivity, and increased dominance. Front Behav Neurosci 2018; 12: 146. [PMID: 30072881 DOI: 10.3389/fnbeh.2018.00146]

[121]

Wang JH, Gessler DJ, Zhan W, Gallagher TL, Gao G. Adeno-associated virus as a delivery vector for gene therapy of human diseases. Sig Transduct Target Ther 2024; 9: 1-33. [DOI: 10.1038/s41392-024-01780-w]

[122]

Wu D, Chen Q, Chen X, Han F, Chen Z, et al. The blood-brain barrier: structure, regulation and drug delivery. Sig Transduct Target Ther 2023; 8: 217. [PMID: 37231000 DOI: 10.1038/s41392-023-01481-w]

[123]

Ndemazie NB, Inkoom A, Morfaw EF, Smith T, Aghimien M, et al. Multi-disciplinary approach for drug and gene delivery systems to the brain. AAPS PharmSciTech 2021; 23: 11. [PMID: 34862567 DOI: 10.1208/s12249-021-02144-1]

[124]

Gao Z. Strategies for enhanced gene delivery to the central nervous system. Nanoscale Adv 2024; 6: 3009-28. [PMID: 38868835 DOI: 10.1039/d3na01125a]

[125]

Riva N, Agosta F, Lunetta C, Filippi M, Quattrini A. Recent advances in amyotrophic lateral sclerosis. J Neurol 2016; 263: 1241-54. [PMID: 27025851 DOI: 10.1007/s00415-016-8091-6]

[126]

Vucic S, Rothstein JD, Kiernan MC. Advances in treating amyotrophic lateral sclerosis: insights from pathophysiological studies. Trends Neurosci 2014; 37: 433-42. [PMID: 24927875 DOI: 10.1016/j.tins.2014.05.006]

[127]

Recabarren-Leiva D, Alarcón M . New insights into the gene expression associated to amyotrophic lateral sclerosis. Life Sci 2018; 193: 110-23. [PMID: 29241710 DOI: 10.1016/j.lfs.2017.12.016]

[128]

Tohnai G, Nakamura R, Sone J, Nakatochi M, Yokoi D, et al. Frequency and characteristics of the TBK1 gene variants in Japanese patients with sporadic amyotrophic lateral sclerosis. Neurobiol Aging 2018; 64: 158.e15-9. [PMID: 29398122 DOI: 10.1016/j.neurobiolaging.2017.12.005]

[129]

Nakevska Z, Yokota T. Challenges and future perspective of antisense therapy for spinal muscular atrophy: a review. Eur J Cell Biol 2023; 102: 151326. [PMID: 37295266 DOI: 10.1016/j.ejcb.2023.151326]

[130]

Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med 2017; 377: 1713-22. [PMID: 29091557 DOI: 10.1056/NEJMoa1706198]

[131]

Aslesh T, Yokota T. Restoring SMN expression: an overview of the therapeutic developments for the treatment of spinal muscular atrophy. Cells 2022; 11: 417. [PMID: 35159227 DOI: 10.3390/cells11030417]

[132]

Qiu J, Wu L, Qu R, Jiang T, Bai J, et al. History of development of the life-saving drug “Nusinersen” in spinal muscular atrophy. Front Cell Neurosci 2022; 16: 942976. [PMID: 36035257 DOI: 10.3389/fncel.2022.942976]

[133]

Haque US, Yokota T. Recent progress in gene-targeting therapies for spinal muscular atrophy: promises and challenges. Genes 2024; 15: 999. [PMID: 39202360 DOI: 10.3390/genes15080999]

PDF (1682KB)

6

Accesses

0

Citation

Detail

Sections
Recommended

/