Astrocytic functions and lipid metabolism: Correlations and therapeutic targets in Alzheimer's disease and glioblastoma

Xu Zhang, Rongrong Gao, Liuke Yang, Youwei Zhu, Tiancheng Zhang, Xiaorong Shen, Wenwen Gu, Long Yang, Shenjie Peng

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Clinical and Translational Discovery ›› 2024, Vol. 4 ›› Issue (2) : e287. DOI: 10.1002/ctd2.287
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Astrocytic functions and lipid metabolism: Correlations and therapeutic targets in Alzheimer's disease and glioblastoma

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Abstract

Background: The brain is a central key organ of the body containing the second highest lipid content only after adipose tissue. Lipids as the main structural components of biological membranes play important roles in a vast number of biological processes within the brain such as energy homeostasis, material transport, signal transduction, neurogenesis and synaptogenesis, providing a balanced cellular environment required for proper functioning of brain cells. Lipids and their metabolism are of great physiological importance in view of the crucial roles of lipids in brain development and function. Astrocytes are the most abundant glial cells in the brain and involved in various processes including metabolic homeostasis, blood brain barrier maintenance, neuronal support and crosstalk.

Results: Disturbances in lipid metabolism and astrocytic functions may lead to pathological alterations associated with numerous neurological diseases like Alzheimer's disease (AD) recognised as the most frequent cause of dementia leading to major progressive memory and cognitive deficits as well as glioblastoma (GBM) known as the most aggressive malignant brain tumour with a poor prognosis.

Conclusions: Herein, we not only review the level and role of altered lipid metabolism in correlation with astrocytic function and astrocyte-neuron crosstalk in AD and GBM, but also discuss important lipid-related metabolites and proteins participating in possible mechanisms of pathologically dysregulated lipid metabolism, offering potential therapeutic targets in targeted molecular therapies for AD and GBM.

Keywords

Alzheimer's disease / astrocyte / glioblastoma / lipid metabolism

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Xu Zhang, Rongrong Gao, Liuke Yang, Youwei Zhu, Tiancheng Zhang, Xiaorong Shen, Wenwen Gu, Long Yang, Shenjie Peng. Astrocytic functions and lipid metabolism: Correlations and therapeutic targets in Alzheimer's disease and glioblastoma. Clinical and Translational Discovery, 2024, 4(2): e287 https://doi.org/10.1002/ctd2.287

References

[1]
LuchtmanDW, SongC. Cognitive enhancement by omega-3 fatty acids from child-hood to old age: findings from animal and clinical studies. Neuropharmacology. 2013;64(Complete):550-565.
[2]
HamiltonJA, Hillard CJ, SpectorAA, WatkinsPA. Brain uptake and utilization of fatty acids, lipids and lipoproteins: application to neurological disorders. J Mol Neurosci. 2007;33(1):2-11.
[3]
LeutiA, FazioD, FavaM, Piccoli A, OddiS. Maccarrone M. Bioactive lipids, inflammation and chronic diseases. Adv Drug Deliv Rev. 2020;159:133-169.
[4]
SubramaniamS, FahyE, GuptaS, et al. Bioinformatics and systems biology of the lipidome. Chem Rev. 2011;111(10):6452-6490.
[5]
HanX. Lipidomics for studying metabolism. Nat Rev Endocrinol. 2016;12(11):668-679.
[6]
LiM, YangL, BaiY, LiuH. Analytical methods in lipidomics and their applications. Anal Chem. 2014;86(1):161-175.
[7]
GaiaC, NicoM, MatteoA, et al. Lipids in the nervous system: from biochemistry and molecular biology to patho-physiology. Biochim Biophys Acta. 2015;1851(1):51-60.
[8]
QiuhuiX, Chunxiu H, DiY, et al. Development of a high coverage pseudotargeted lipidomics method based on ultra-high performance liquid chromatography-mass spectrometry. Anal Chem. 2018;90(12):7608-7616.
[9]
WoodPL, CebakJE. Lipidomics biomarker studies: errors, limitations, and the future. Biochem Biophys Res Commun. 2018:S6291X-S18307101X.
[10]
RustamYH, ReidGE. Analytical challenges and recent advances in mass spectrometry based lipidomics. Anal Chem. 2017:7b-4836b.
[11]
ChavesED, Rusinol AE, VanceDE, CampenotRB, VanceJE. Role of lipoproteins in the delivery of lipids to axons during axonal regeneration. J Biol Chem. 1997;272(49):30766.
[12]
FesterL, ZhouL, BütowA, et al. Cholesterol-promoted synaptogenesis requires the conversion of cholesterol to estradiol in the hippocampus. Hippocampus. 2009;19(8):692-705.
[13]
SangN. Lipid signaling and synaptic plasticity. Neuroscientist. 2006;12(5):425-434.
[14]
HussainG, WangJ, RasulA, et al. Role of cholesterol and sphingolipids in brain development and neurological diseases. Lipids Health Dis. 2019;18(1):26.
[15]
JorgeC, FarezMF. The role of astrocytes in multiple sclerosis progression. Front Neurol. 2015;6(180):180.
[16]
JoeEH, ChoiDJ, AnJ, EunJH, JouI, ParkS. Astrocytes, microglia, and Parkinson's disease. Exp Neurobiol. 2018;27(2):77-87.
[17]
AlmadA, Maragakis NJ. A stocked toolbox for understanding the role of astrocytes in disease. Nat Rev Neurol. 2018;14(6):351-362.
[18]
BelangerM, Allaman I, MagistrettiPJ. Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab. 2011;14(6):724-738.
CrossRef Google scholar
[19]
UllianEM. Control of synapse number by glia. Science. 2001;291(5504):657.
[20]
VarciannaA, Myszczynska MA, CastelliLM, et al. Micro-RNAs secreted through astrocyte-derived extracellular vesicles cause neuronal network degeneration in C9orf72 ALS. EBioMedicine. 2019;40:626-635.
[21]
ChungWS, AllenNJ, ErogluC. Astrocytes control synapse formation, function, and elimination. Cold Spring Harbor Perspect Biol. 2015;7(9):a020370.
[22]
SofroniewMV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010;119(1):7-35.
[23]
DeitmerJW, Theparambil SM, RuminotI, NoorSI, BeckerHM. Energy dynamics in the brain: contributions of astrocytes to metabolism and pH homeostasis. Front Neurosci. 2019;13:1301.
[24]
BallabhP, BraunA, NedergaardM. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Int J Cerebrovasc Dis. 2004;16(1):1-13.
[25]
AbbottNJ, Patabendige AAK, DolmanDEM, YusofSR, BegleyDJ. Structure and function of the blood–brain barrier. Neurobiol Dis. 2010;37(1):13-25.
CrossRef Google scholar
[26]
EdmondJ. Essential polyunsaturated fatty acids and the barrier to the brain. J Mol Neurosci. 2001;16(2-3):181-193.
[27]
MitchellRW, HatchGM. Fatty acid transport into the brain: of fatty acid fables and lipid tails. Prostaglandins Leukot Essent Fatty Acids. 2011;85(5):293-302.
[28]
SaundersNR, EkCJ, HabgoodMD, Dziegielewska KM. Barriers in the brain: a renaissance? Trends Neurosci. 2008;31(6):279-286.
[29]
BradburyMW. The structure and function of the blood-brain barrier. Fed Proc. 1984;43(2):186-190.
[30]
BetsholtzC. Physiology: double function at the blood brain barrier. Nature. 2014;509(7501):432-433.
[31]
DanemanR, PratA. The blood–brain barrier. Cold Spring Harbor Perspect Biol. 2015;7(1):32-34.
[32]
FerreiraL. What human blood-brain barrier models can tell us about BBB function and drug discovery? Expert Opin Drug Dis. 2019;14(29):1-11.
[33]
MouraRP, Martins C, PintoS, SousaF, Sarmento B. Blood-brain barrier receptors and transporters: an insight on their function and how to exploit them through nanotechnology. Expert Opin Drug Deliv. 2019;16(3):271-285.
[34]
DienelGA, CruzNF. Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism. J Neurochem. 2016;138(1):14-52.
[35]
GoyalMS, Hawrylycz M, MillerJA, SnyderAZ, Raichle ME. Aerobic glycolysis in the human brain is associated with development and neotenous gene expression. Cell Metab. 2014;19(1):49-57.
[36]
AbeT, Takahashi S, SuzukiN. Oxidative metabolism in cultured rat astroglia: effects of reducing the glucose concentration in the culture medium and of D-aspartate or potassium stimulation. J Cereb Blood Flow Metab. 2006;26(2):153-160.
[37]
CataldoAM, Broadwell RD. Cytochemical identification of cerebral glycogen and glucose-6-phosphatase activity under normal and experimental conditions. II. Choroid plexus and ependymal epithelia, endothelia and pericytes. J Neurocytol. 1986;15(4):511-524.
[38]
Pfeiffer-GuglielmiB, Fleckenstein B, JungG, HamprechtB. Immunocytochemical localization of glycogen phosphorylase isozymes in rat nervous tissues by using isozyme-specific antibodies. J Neurochem. 2010;85(1):73-81.
[39]
CamargoN, Goudriaan A, DeijkALFV, OtteWM, Verheijen MHG. Oligodendroglial myelination requires astrocyte-derived lipids. PLoS Biol. 2017;15(5):e1002605.
[40]
Van DeijkALF, Camargo N, TimmermanJ, et al. Astrocyte lipid metabolism is critical for synapse development and function in vivo. Glia. 2017;65(4):670-682.
[41]
IoannouMS, JesseJ, Shu-HsienS, et al. Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity. Cell. 2020;177(6):1522-1535.
[42]
EbertD, HallerRG, WaltonME. Energy contribution of octanoate to intact rat brain metabolism measured by 13C nuclear magnetic resonance spectroscopy. J Neurosci. 2003;23(13):5928.
[43]
ChangCY, KeDS, ChenJY. Essential fatty acids and human brain. Acta Neurol Taiwan. 2009;18(4):231-241.
[44]
EdmondJ, Robbins RA, BergstromJD, ColeRA, VellisJD. Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture. J Neurosci Res. 2010;18(4):551-561.
[45]
TakahashiS, IizumiT, MashimaK, Abe T, SuzukiN. Roles and regulation of ketogenesis in cultured astroglia and neurons under hypoxia and hypoglycemia. ASN Neuro. 2014;6(5):1759091414550997.
[46]
SimardJR, PillaiBK, HamiltonJA. Fatty acid flip-flop in a model membrane is faster than desorption into the aqueous phase. Biochemistry. 2008;47(35):9081.
[47]
MitchellRW, OnNH, BigioMRD, Miller DW, HatchGM. Fatty acid transport protein expression in human brain and potential role in fatty acid transport across human brain microvessel endothelial cells. J Neurochem. 2011;117(4):735-746.
[48]
MarianneH. Essential fatty acids and the brain. Can J Psychiatry. 2003;48(3):195-203.
[49]
TraceyTJ, SteynFJ, WolvetangEJ, Ngo ST. Neuronal lipid metabolism: multiple pathways driving functional outcomes in health and disease. Front Mol Neurosci. 2018;11:10.
[50]
CrawfordMA, Casperd NM, SinclairAJ. The long chain metabolites of linoleic and linolenic acid in liver and brain in herbivores and carnivores. Comp Biochem Physiol B. 1976;54(3):395-401.
[51]
CrawfordMA, Broadhurst CL, GuestM, et al. A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution. Prostaglandins Leukot Essent Fatty Acids. 2013;88(1):5-13.
[52]
BazinetRP, LayS. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci. 2014;15(12):771-785.
[53]
LuchtmanDW, SongC. Cognitive enhancement by omega-3 fatty acids from child-hood to old age: findings from animal and clinical studies. Neuropharmacology. 2013;64(Complete):550-565.
[54]
DenisI, PotierB, VancasselS, Heberden C, LavialleM. Omega-3 fatty acids and brain resistance to ageing and stress: body of evidence and possible mechanisms. Ageing Res Rev. 2013;12(2):579-594.
[55]
IgarashiM, SantosRA, Cohen-CoryS. Impact of maternal n-3 polyunsaturated fatty acid deficiency on dendritic arbor morphology and connectivity of developing Xenopus laevis central neurons in vivo. J Neurosci. 2015;35(15):6079-6092.
[56]
LimGP, CalonF, MoriharaT, et al. A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci. 2005;25(12):3032.
[57]
MichaelAC. Docosahexaenoic acid in neural signaling systems. Nutr Health. 2006;18(3):263-276.
[58]
HamiltonJA, Hillard CJ, SpectorAA, WatkinsPA. Brain uptake and utilization of fatty acids, lipids and lipoproteins: application to neurological disorders. J Mol Neurosci. 2007;33(1):2-11.
[59]
FarooquiAA, Horrocks LA, FarooquiT. Glycerophospholipids in brain: their metabolism, incorporation into membranes, functions, and involvement in neurological disorders. Chem Phys Lipids. 2000;106(1):1-29.
[60]
VanMG, Voelker DR, FeigensonGW. Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol. 2008;9(2):112-124.
[61]
HarayamaT, Riezman H. Understanding the diversity of membrane lipid composition. Nat Rev Mol Cell Biol. 2018;19(5):281-296.
[62]
LiJ, WangX, ZhangT, et al. A review on phospholipids and their main applications in drug delivery systems. Asian J Pharm Sci. 2015;10(2):81-98.
[63]
RossBM, Moszczynska A, BlusztajnJK, SherwinA, LozanoA, KishSJ. Phospholipid biosynthetic enzymes in human brain. Lipids. 1997;32(4):351-358.
[64]
HannaCC, Kriegesmann J, DowmanLJ, BeckerCFW, PayneRJ. Chemical Synthesis and Semisynthesis of Lipidated Proteins. Angew Chem Int Ed Engl. 2022;61(15):e202111266.
[65]
TraceyTJ, SteynFJ, WolvetangEJ, Ngo ST. Neuronal lipid metabolism: multiple pathways driving functional outcomes in health and disease. Front Mol Neurosci. 2018;11:10.
[66]
AneleyM, ThemisT, SilvaD, et al. Author correction: specific phospholipids regulate the acquisition of neuronal and astroglial identities in Post-Mitotic cells. Sci Rep. 2019;9(1):20222.
[67]
SonninoS, Prinetti A. Membrane domains and the lipid raft concept. Curr Med Chem. 2012;20(1):4-21.
[68]
West RJH, BriggsL, FjeldstadMP, Ribchester RR, SweeneyST. Sphingolipids regulate neuromuscular synapse structure and function in drosophila. J Comp Neurol. 2018;526(13):1995-2009.
[69]
VanceDE. Biochemistry of lipids, lipoproteins and membranes (Fifth edition). Elsevier; 2008:v-vi.
[70]
HannunYA, ObeidLM. Sphingolipids and their metabolism in physiology and disease. Nat Rev Mol Cell Biol. 2018;19(3):175-191.
[71]
SchnaarRL. Gangliosides of the vertebrate nervous system. J Mol Biol. 2016;3325-3336.
[72]
NovgorodovSA, VoltinJR, WangW, Tomlinson S, RileyCL, GudzTI. Acid sphingomyelinase deficiency protects mitochondria and improves function recovery after brain injury. J Lipid Res. 2019;60(3):609-623.
[73]
HartmannD, LucksJ, FuchsS, et al. Long chain ceramides and very long chain ceramides have opposite effects on human breast and colon cancer cell growth. Int J Biochem Cell Biol. 2012;44(4):620-628.
[74]
XuR, WangK, MilevaI, Hannun YA, ObeidLM, MaoC. Alkaline ceramidase 2 and its bioactive product sphingosine are novel regulators of the DNA damage response. Oncotarget. 2016;7(14):18440-18457.
[75]
Gomez-Mu OzA, PresaN, Gomez-LarrauriA, RiveraIG, TruebaM, Ordo EzM. Control of inflammatory responses by ceramide, sphingosine 1-phosphate and ceramide 1-phosphate. Prog Lipid Res. 2016:51-62.
[76]
BlomT, Somerharju P, IkonenE. Synthesis and biosynthetic trafficking of membrane lipids. Cold Spring Harbor Perspect Biol. 2011;3(8):a4713.
[77]
BjorkhemI. Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol. 2004;24(5):806-815.
[78]
KangS, KimCH, JungH, Kim E, SongHT, LeeJE. Agmatine ameliorates type 2 diabetes induced-Alzheimer's disease-like alterations in high-fat diet-fed mice via reactivation of blunted insulin signalling. Neuropharmacology. 2017;113(Pt A):467-479.
[79]
SaeedAA, GenoveG, LiT, et al. Effects of a disrupted Blood-Brain barrier on cholesterol homeostasis in the brain. J Biol Chem. 2014;289(34):23712-23722.
[80]
ReinhartMP, Billheimer JT, FaustJR, GaylorJL. Subcellular localization of the enzymes of cholesterol biosynthesis and metabolism in rat liver. J Biol Chem. 1987;262(20):9649.
[81]
MuseED, Jurevics H, ToewsAD, MatsushimaGK, MorellP. Parameters related to lipid metabolism as markers of myelination in mouse brain. J Neurochem. 2010;76(1):77-86.
[82]
ZarroukA, Debbabi M, BezineM, et al. Lipid biomarkers in Alzheimer's disease. Curr Alzheimer Res. 2018;15(4):303-312.
[83]
Genaro-MattosTC, Anderson A, AllenLB, KoradeZ, Mirnics K. Cholesterol biosynthesis and uptake in developing neurons. ACS Chem Neurosci. 2019;10(8):3671-3681.
[84]
van DeijkAF, Camargo N, TimmermanJ, et al. Astrocyte lipid metabolism is critical for synapse development and function in vivo. Glia. 2017;65(4):670-682.
[85]
WangH, EckelRH. What are lipoproteins doing in the brain? Trends Endocrinol Metab. 2014;25(1):8-14.
[86]
OrthM, Bellosta S. Cholesterol: its regulation and role in central nervous system disorders. Cholesterol. 2012;2012:292598.
[87]
PitasRE, BoylesJK, LeeSH, Hui D, WeisgraberKH. Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain. J Biol Chem. 1987;262(29):14352-14360.
[88]
JingC, ZhangX, KusumoH, Costa LG, GuizzettiM. Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis. Biochim Biophys Acta. 2013;1831(2):263-275.
[89]
RushworthJV, HooperNM. Lipid rafts: linking alzheimer's amyloid-beta production, aggregation, and toxicity at neuronal membranes. Int J Alzheimer's Dis. 2010;2011(3):603052.
[90]
KabouridisPS, JanzenJ, MageeAL, Ley SC. Cholesterol depletion disrupts lipid rafts and modulates the activity of multiple signaling pathways in T lymphocytes. Eur J Immunol. 2015;30(3):954-963.
[91]
PikeLJ. Lipid rafts bringing order to chaos. J Lipid Res. 2003;44(4):655-667.
[92]
HussainG, WangJ, RasulA, et al. Role of cholesterol and sphingolipids in brain development and neurological diseases. Lipids Health Dis. 2019;18(1):26.
[93]
MauchDH, Nägler K, SchumacherS, et al. CNS synaptogenesis promoted by glia-derived cholesterol. Science. 2001;294(5545):1354-1357.
[94]
FukuiK, FerrisHA, KahnCR. Effect of cholesterol reduction on receptor signaling in neurons. J Biol Chem. 2015:26383-26392.
[95]
ChavesED, Rusinol AE, VanceDE, CampenotRB, VanceJE. Role of lipoproteins in the delivery of lipids to axons during axonal regeneration. J Biol Chem. 1997;272(49):30766.
[96]
Xue-ShanZ, JuanP, QiW, et al. Imbalanced cholesterol metabolism in Alzheimer's disease. Clin Chim Acta. 2016;456:107-114.
[97]
KandimallaR, Thirumala V, ReddyPH. Is Alzheimer's disease a type 3 diabetes? A critical appraisal. Biochim Biophys Acta. 2016;1863(5):1078-1089.
[98]
SonninoS, Prinetti A. Membrane domains and the “lipid raft” concept. Curr Med Chem. 2013;20(1):4-21.
[99]
CalicetiC, Zambonin L, PrataC, et al. Effect of plasma membrane cholesterol depletion on glucose transport regulation in leukemia cells. PLoS One. 2012;7(7):e41246.
[100]
Banach-OrłowskaM, WyszyńskaR, Pyrzyńska B, MaksymowiczM, GołąbJ, Miączyńska M. Cholesterol restricts lymphotoxin β receptor-triggered NF-κB signaling. Cell Commun Signal. 2019;17(1):171.
[101]
ZhangJ, LiQ, WuY, et al. Cholesterol content in cell membrane maintains surface levels of ErbB2 and confers a therapeutic vulnerability in ErbB2-positive breast cancer. Cell Commun Signal. 2019;17(1):15.
[102]
WollerSA, ChoiS, AnEJ, et al. Inhibition of neuroinflammation by AIBP: spinal effects upon facilitated pain states. Cell Rep. 2018;23(9):2667-2677.
CrossRef Google scholar
[103]
ZhuX, OwenJS, WilsonMD, et al. Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol. J Lipid Res. 2010;51(11):3196-3206.
[104]
GhoshS, StrumJC, BellRM. Lipid biochemistry: functions of glycerolipids and sphingolipids in cellular signaling. FASEB J. 1997;11(1):45.
[105]
AlaupovicP. Significance of apolipoproteins for structure, function, and classification of plasma lipoproteins. Meth Enzymol. 1996;263(263):32-60.
[106]
HoofnagleAN, Heinecke JW. Lipoproteomics: using mass spectrometry-based proteomics to explore the assembly, structure, and function of lipoproteins. J Lipid Res. 2009;50(10):1967-1975.
[107]
BraunV, HantkeK. Lipoproteins: structure, function, biosynthesis. Subcell Biochem. 2019;92:39-77.
[108]
BalazsZ, Panzenboeck U, HammerA, et al. Uptake and transport of high-density lipoprotein (HDL) and HDL-associated alpha-tocopherol by an in vitro blood-brain barrier model. J Neurochem. 2010;89(4):939-950.
[109]
PitasRE, BoylesJK, LeeSH, Foss D, MahleyRW. Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins. Biochim Biophys Acta. 1987;917(1):148-161.
[110]
FeingoldKR. Introduction to Lipids and Lipoproteins. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2024;2000.
[111]
ItoJI, Nagayasu Y, MiuraY, YokoyamaS, Michikawa M. Astrocytes endogenous apoE generates HDL-like lipoproteins using previously synthesized cholesterol through interaction with ABCA1. Brain Res. 2014;1570:1-12.
[112]
Bolanos-GarciaVM, Miguel RN. On the structure and function of apolipoproteins: more than a family of lipid-binding proteins. Prog Biophys Mol Biol. 2003;83(1):47-68.
[113]
FilouS, LhommeM, KaraviaEA, et al. Distinct roles of apolipoproteins A1 and E in the modulation of high-density lipoprotein composition and function. Biochemistry. 2016;55(27):3752-3762.
[114]
RamasamyI. Recent advances in physiological lipoprotein metabolism. Clin Chem Lab Med. 2014;52(12):1695-1727.
[115]
DienelGA, CruzNF. Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism. J Neurochem. 2016;138(1):14-52.
[116]
DienelGA. Brain glucose metabolism: integration of energetics with function. Physiol Rev. 2019;99(1):949-1045.
[117]
GoyalMS, Hawrylycz M, MillerJA, SnyderAZ, Raichle ME. Aerobic glycolysis in the human brain is associated with development and neotenous gene expression. Cell Metab. 2014;19(1):49-57.
[118]
AbeT, Takahashi S, SuzukiN. Oxidative metabolism in cultured rat astroglia: effects of reducing the glucose concentration in the culture medium and of D-aspartate or potassium stimulation. J Cereb Blood Flow Metab. 2006;26(2):153-160.
[119]
ZhangY, ChenK, SloanSA, et al. An RNA-Sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci. 2014;34(36):11929-11947.
[120]
SharmaK, Schmitt S, BergnerCG, et al. Cell type-and brain region-resolved mouse brain proteome. Nat Neurosci. 2015;18(12):1819-1831.
[121]
AfridiR, KimJH, RahmanMH, Suk K. Metabolic regulation of glial phenotypes: implications in neuron-glia interactions and neurological disorders. Front Cell Neurosci. 2020;14:20.
[122]
AlexeiV, Vladimir P, NinaV, et al. Physiology of astroglia. Adv Exp Med Biol. 2019;1175:45-91.
[123]
MagistrettiPPJ. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci USA. 1994;91(22):10625-10629.
[124]
MagistrettiPJ, Allaman I. Lactate in the brain: from metabolic end-product to signalling molecule. Nat Rev Neurosci. 2018;19(4):235-249.
[125]
LiuL, Mackenzie KR, PutluriN, Maleti-SavatiM, BellenHJ. The glia-neuron lactate shuttle and elevated ROS promote lipid synthesis in neurons and lipid droplet accumulation in glia via APOE/D. Cell Metab. 2017:719-737.
[126]
IoannouMS, Jackson J, SheuSH, ChangCL, LiuZ. Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity. Cell. 2019;177(6).
[127]
YoonH, ShawJL, HaigisMC, Greka A. Lipid metabolism in sickness and in health: emerging regulators of lipotoxicity. Mol Cell. 2021;81(18):3708-3730.
[128]
LiuL, ZhangK, SandovalH, et al. Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell. 2015;160(1-2):177-190.
[129]
OlzmannJA, Carvalho P. Dynamics and functions of lipid droplets. Nat Rev Mol Cell Biol. 2019;20(3):137-155.
[130]
WaltherTC, ChungJ, FareseRV. Lipid droplet biogenesis. Annu Rev Cell Dev Biol. 2017;33:491-510.
[131]
FaganAM, Holtzman DM. Astrocyte lipoproteins, effects of APOE on neuronal function, and role of APOE in amyloid-beta deposition in vivo. Microsc Res Tech. 2000;50(4):297-304.
[132]
BiW, LeiT, CaiS, et al. Potential of astrocytes in targeting therapy for Alzheimer's disease. Int Immunopharmacol. 2022;113(Pt A):109368.
[133]
GuttenplanKA, WeigelMK, PrakashP, et al. Neurotoxic reactive astrocytes induce cell death via saturated lipids. Nature. 2021;599(7883):102-107.
[134]
VerdugoE, PuertoI, MedinaMÁ. An update on the molecular biology of glioblastoma, with clinical implications and progress in its treatment. Cancer Commun (Lond). 2022;42(11):1083-1111.
[135]
MiY, QiG, VitaliF, et al. Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration. Nat Metab. 2023;5(3):445-465.
[136]
QiG, MiY, ShiX, GuH, BrintonRD, Yin F. ApoE4 impairs neuron-astrocyte coupling of fatty acid metabolism. Cell Rep. 2021;34(1):108572.
[137]
RlhhA, CagwA, PaA, MajB, FrjvA, Jls C. Diagnosing Alzheimer's disease: a systematic review of economic evaluations - ScienceDirect. Alzheimers Dement. 2014;10(2):225-237.
[138]
BrookmeyerR, EvansDA, HebertL, et al. National estimates of the prevalence of Alzheimer's disease in the United States. Alzheimers Dement. 2011;7(1):61-73.
[139]
2022 Alzheimer's disease facts and figures. Alzheimers Dement. 2022;18(4):700-789.
[140]
MastersCL, Beyreuther K. Alzheimer's disease. BMJ. 1998;316(7129):446-448.
[141]
MattsonMP. Pathways towards and away from Alzheimer's disease. Nature. 2016;430(7000):631-639.
[142]
VishalS, Sourabh A, HarkiratS. Alois Alzheimer (1864-1915) and the Alzheimer syndrome. J Med Biogr. 2011;19(1):32-33.
[143]
d'ErricoP, Meyer-Luehmann M. Mechanisms of pathogenic Tau and Aβ protein spreading in Alzheimer's disease. Front Aging Neurosci. 2020;12:265.
[144]
BraakH, BraakE. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239-259.
[145]
El KadmiriN, SaidN, SlassiI, El Moutawakil B, NadifiS. Biomarkers for Alzheimer disease: classical and novel candidates' review. Neuroscience. 2018;370:181-190.
[146]
HardyJ, AllsopD. Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol Sci. 1991;12(10):383-388.
[147]
StandaertDG, LeeVM, GreenbergBD, Lowery DE, TrojanowskiJQ. Molecular features of hypothalamic plaques in Alzheimer's disease. Am J Pathol. 1991;139(3):681-691.
[148]
HardyJA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science. 1992;256(5054):184-185.
[149]
SelkoeDJ. Alzheimer's disease is a synaptic failure. Science. 2002;298(5594):789-791.
[150]
WalshDM, SelkoeDJ. Deciphering the molecular basis of memory failure in Alzheimer's disease. Neuron. 2004;44(1):181-193.
[151]
GoedertM, Spillantini MG, JakesR, RutherfordD, Crowther RA. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron. 1989;3(4):519-526.
[152]
BraakH, BraakE. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239-259.
[153]
LeeVM, Goedert M, TrojanowskiJQ. Neurodegenerative tauopathies. Annu Rev Neurosci. 2001;24:1121-1159.
[154]
GoedertM, Spillantini MG. A century of Alzheimer's disease. Science. 2006;314(5800):777-781.
[155]
BallatoreC, LeeVM, TrojanowskiJQ. Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat Rev Neurosci. 2007;8(9):663-672.
[156]
IttnerLM, Götz J. Amyloid-β and tau–a toxic pas de deux in Alzheimer's disease. Nat Rev Neurosci. 2011;12(2):65-72.
[157]
HenekaMT, CarsonMJ, El KhouryJ, et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol. 2015;14(4):388-405.
[158]
AkiyamaH, BargerS, BarnumS, et al. Inflammation and Alzheimer's disease. Neurobiol Aging. 2000;21(3):383-421.
[159]
FoleyP. Lipids in Alzheimer's disease: a century-old story. Biochim Biophys Acta. 2010;1801(8):750-753.
[160]
AlzheimerA. Uber eine eigenartige Erkrankung der Hirnride. Allg.z.psychiatr. 1907.
[161]
KimM, Nevado-Holgado A, WhileyL, et al. Association between plasma ceramides and phosphatidylcholines and hippocampal brain volume in late onset Alzheimer's disease. J Alzheimers Dis. 2017;60(3):809-817.
[162]
González-DomínguezR, García-BarreraT, Vitorica J, Gómez-ArizaJL. Metabolomic screening of regional brain alterations in the APP/PS1 transgenic model of Alzheimer's disease by direct infusion mass spectrometry. J Pharmaceut Biomed. 2015;102:425-435.
[163]
BennettS, Valenzuela N, XuH, FrankoB, FaiS, FigeysD. Using neurolipidomics to identify phospholipid mediators of synaptic (dys)function in Alzheimer's Disease. Front Physiol. 2013;4:168.
[164]
KaoYC, HoPC, TuYK, JouIM, TsaiKJ. Lipids and alzheimer's disease. Int J Mol Sci. 2020;21(4):1505.
[165]
GrimmMOW, Michaelson DM, HartmannT. Omega-3 fatty acids, lipids, and apoE lipidation in Alzheimer's disease: a rationale for multi-nutrient dementia prevention. J Lipid Res. 2017;58(11):2083-2101.
[166]
WoodPL. Lipidomics of Alzheimer's disease: current status. Alzheimers Res Ther. 2012;4(1):5.
[167]
BalesKR. Brain lipid metabolism, apolipoprotein E and the pathophysiology of Alzheimer's disease. Neuropharmacology. 2010;59(4-5):295-302.
[168]
LedesmaMD, MartinMG, DottiCG. Lipid changes in the aged brain: effect on synaptic function and neuronal survival. Prog Lipid Res. 2012;51(1):23-35.
[169]
SultanaR, Perluigi M, Allan ButterfieldD. Lipid peroxidation triggers neurodegeneration: a redox proteomics view into the Alzheimer disease brain. Free Radical Biol Med. 2013;62:157-169.
[170]
ZhuTB, ZhangZ, LuoP, et al. Lipid metabolism in Alzheimer's disease. Brain Res Bull. 2019;144:68-74.
[171]
NasaruddinML, Hölscher C, KehoeP, GrahamSF, GreenBD. Wide-ranging alterations in the brain fatty acid complement of subjects with late Alzheimer's disease as detected by GC-MS. Am J Transl Res. 2016;8(1):154-165.
[172]
NasaruddinML, PanX, McGuinnessB, et al. Evidence that parietal lobe fatty acids may be more profoundly affected in moderate Alzheimer's disease (AD) pathology than in severe AD pathology. Metabolites. 2018;8(4):69.
[173]
WoodPL, Barnette BL, KayeJA, QuinnJF, Woltjer RL. Non-targeted lipidomics of CSF and frontal cortex grey and white matter in control, mild cognitive impairment, and Alzheimer's disease subjects. Acta Neuropsychiatr. 2015;27(05):270-278.
[174]
BelkouchM, HachemM, ElgotA, et al. The pleiotropic effects of omega-3 docosahexaenoic acid on the hallmarks of Alzheimer's disease. J Nutr Biochem. 2016;38:1-11.
[175]
SarrafpourS, Ormseth C, ChiangA, ArakakiX, Harrington M, FontehA. Lipid metabolism in late-onset alzheimer's disease differs from patients presenting with other dementia phenotypes. Int J Env Res Pub He. 2019;16(11):1995.
CrossRef Google scholar
[176]
WongMW, BraidyN, PoljakA, Pickford R, ThambisettyM, SachdevPS. Dysregulation of lipids in Alzheimer's disease and their role as potential biomarkers. Alzheimers Dement. 2017;13(7):810-827.
[177]
XiongH, Callaghan D, JonesA, et al. Cholesterol retention in Alzheimer's brain is responsible for high - and secretase activities and a production. Neurobiol Dis. 2008;29(3):422-437.
[178]
PfriegerFW. Cholesterol homeostasis and function in neurons of the central nervous system. Cell Mol Life Sci. 2003:1158-1171.
[179]
ChangTY, Yamauchi Y, HasanMT, ChangC. Cellular cholesterol homeostasis and Alzheimer's disease. J Lipid Res. 2017;58(12):2239-2254.
[180]
Di ScalaC, Chahinian H, YahiN, GarmyN, Fantini J. Interaction of Alzheimer's β-amyloid peptides with cholesterol: mechanistic insights into amyloid pore formation. Biochemistry. 2014;53(28):4489-4502.
[181]
Area-GomezE, MariaDCLC, TambiniMD, et al. Upregulated function of mitochondria-associated ER membranes in Alzheimer disease. EMBO J. 2012;31(21):4106-4123.
[182]
Area-GomezE, SchonEA. Mitochondria-associated ER membranes and Alzheimer disease. Curr Opin Genet Dev. 2016;38(10):90-96.
[183]
PeraM, LarreaD, Guardia-LaguartaC, et al. Increased localization of APP-C99 in mitochondria-associated ER membranes causes mitochondrial dysfunction in Alzheimer disease. EMBO J. 2017;36(22):3356-3371.
[184]
PeraM, Montesinos J, LarreaD, et al. MAM and C99, key players in the pathogenesis of Alzheimer's disease. Int Rev Neurobiol. 2020;154:235-278.
[185]
BaileyAP, KosterG, GuillermierC, et al. Antioxidant role for lipid droplets in a stem cell niche of drosophila. Cell. 2015;163(2):340-353.
[186]
LiuL, ZhangK, SandovalH, et al. Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell. 2015;160(1-2):177-190.
[187]
LiuL, Mackenzie KR, PutluriN, Maleti-SavatiM, BellenHJ. The glia-neuron lactate shuttle and elevated ROS promote lipid synthesis in neurons and lipid droplet accumulation in glia via APOE/D. Cell Metab. 2017:719-737.
[188]
WongMW, BraidyN, PoljakA, Sachdev PS. The application of lipidomics to biomarker research and pathomechanisms in Alzheimer's disease. Curr Opin Psychiatr. 2017;30(2):136-144.
[189]
ZhangAH, MaZM, KongL, et al. High-throughput lipidomics analysis to discover lipid biomarkers and profiles as potential targets for evaluating efficacy of Kai-Xin-San against APP/PS1 transgenic mice based on UPLC-Q/TOF-MS. Biomed Chromatogr. 2020;34(2):e4724.
[190]
BarupalDK, Baillie R, FanS, SaykinAJ, Kaddurah-Daouk R. Sets of coregulated serum lipids are associated with Alzheimer's disease pathophysiology. Alzheimers Dement. 2019;11(1):619-627.
[191]
ZhaoN, LiuCC, QiaoW, Bu G. Apolipoprotein E, receptors, and modulation of Alzheimer's disease. Biol Psychiatry. 2018;83(4):347-357.
[192]
Monteiro-CardosoVF, Oliveira MM, MeloT, DominguesMRM, Videira RA. Cardiolipin profile changes are associated to the early synaptic mitochondrial dysfunction in Alzheimer's disease. J Alzheimers Dis. 2015;43(4):1375.
[193]
Basu BallW, NeffJK, GohilVM. The role of nonbilayer phospholipids in mitochondrial structure and function. Febs Lett. 2017;592(8):1273-1290.
CrossRef Google scholar
[194]
CalzadaE, OngukaO, ClaypoolSM. Phosphatidylethanolamine metabolism in health and disease. Int Rev Cel Mol Bio. 2016;321:29-88.
[195]
FontehAN, Cipolla M, ChiangJ, ArakakiX, Harrington MG. Human cerebrospinal fluid fatty acid levels differ between supernatant fluid and Brain-Derived nanoparticle fractions, and are altered in Alzheimer's disease. PLoS One. 2014;9(6):e100519.
[196]
GiudettiAM, ShuG, VergaraD, Fonteh AN. Polyunsaturated fatty acid composition of cerebrospinal fluid fractions shows their contribution to cognitive resilience of a pre-symptomatic Alzheimer's disease cohort. Front Physiol. 2020;11(33):1-14.
[197]
WildeMD, VellasB, GiraultE, Yavuz AC, SijbenJW. Lower brain and blood nutrient status in Alzheimer's disease: results from meta-analyses. Alzheimers Dement. 2017;3(3):416-431.
[198]
SnowdenSG, Ebshiana AA, HyeA, AnY, Thambisetty M. Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: a nontargeted metabolomic study. PLoS Med. 2017;14(3).
[199]
HosseiniM, PoljakA, BraidyN, Crawford J, SachdevP. Blood fatty acids in Alzheimer's disease and mild cognitive impairment: a meta-analysis and systematic review. Ageing Res Rev. 2020;60:101043.
[200]
WoodPL, Barnette BL, KayeJA, QuinnJF, Woltjer RL. Non-targeted lipidomics of CSF and frontal cortex grey and white matter in control, mild cognitive impairment, and Alzheimer's disease subjects. Acta Neuropsychiatr. 2015;27(05):270-278.
[201]
DyallSC. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Front Aging Neurosci. 2015;7:52.
[202]
IorioD, Bartali B, CorsiA, BandinelliS, Mattson MP, FerrucciL. Low plasma N-3 fatty acids and dementia in older persons: the InCHIANTI study. J Gerontol A Biol Med. 2007;62(10):1120-1126.
[203]
ThomasMH, Pelleieux S, VitaleN, OlivierJL. Dietary arachidonic acid as a risk factor for age-associated neurodegenerative diseases: potential mechanisms. Biochimie. 2016:168-177.
[204]
GoozeeK, Chatterjee P, JamesI, et al. Alterations in erythrocyte fatty acid composition in preclinical Alzheimer's disease. Sci Rep. 2017;7(1):676.
[205]
PrasadMR, LovellMA, YatinM, Dhillon H, MarkesberyWR. Regional membrane phospholipid alterations in Alzheimer's disease. Neurochem Res. 1998;23(1):81-88.
[206]
CunnaneSC, Schneider JA, TangneyC, Tremblay-MercierJ, Morris MC. Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer's disease. J Alzheimer's Dis. 2012;29(3):691-697.
[207]
IwamotoN, Kobayashi K, KosakaK. The formation of prostaglandins in the postmortem cerebral cortex of Alzheimer-type dementia patients. J Neurol. 1989;236(2):80-84.
[208]
WoodPL. Lipidomics of Alzheimer's disease: current status. Alzheimers Res Ther. 2012;4(1):5.
[209]
FontehAN, ChiangJ, CipollaM, et al. Alterations in cerebrospinal fluid glycerophospholipids and phospholipase A2 activity in Alzheimer's disease. J Lipid Res. 2013;54(10):2884-2897.
[210]
WhileyL, SenA, HeatonJ, et al. Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease. Neurobiol Aging. 2014;35(2):271-278.
[211]
GuanZ, WangY, CairnsNJ, Lantos PL, GustavD, SindelarPJ. Decrease and structural modifications of phosphatidylethanolamine plasmalogen in the brain with alzheimer disease. J Neuropathol Exp Neurol. 1999;58(7):740-747.
[212]
FarooquiAA, Horrocks LA. Plasmalogen-selective phospholipase A2 and its involvement in Alzheimer's disease. Biochem Soc T. 1998;26(2):243.
[213]
FilippovV, SongMA, ZhangK, Vinters HV, Duerksen-HughesPJ. Increased ceramide in brains with alzheimer's and other neurodegenerative diseases. J Alzheimers Dis. 2012;29(3):537-547.
[214]
FontehAN, Ormseth C, ChiangJ, CipollaM, Arakaki X, HarringtonMG. Sphingolipid metabolism correlates with cerebrospinal fluid Beta amyloid levels in Alzheimer's disease. PLoS One. 2015;10(5):e0125597.
[215]
LeparaO, Valjevac A, AlajbegoviA, ZairagiA, Nakas-I indi E. Decreased serum lipids in patients with probable Alzheimer's disease. Bosnian J Basic Med Sci. 2009;9(3):215-220.
[216]
BernathMM, Bhattacharyya S, NhoK, et al. Alzheimer's disease neuroimaging initiative and Alzheimer's disease metabolomics consortium. Serum triglycerides in Alzheimer disease: relation to neuroimaging and CSF biomarkers. Neurology. 2020;94(20):e2088-e2098.
[217]
HascaloviciJR, VayaJ, KhatibS, Holcroft CA, SchipperHM. Brain sterol dysregulation in sporadic AD and MCI: relationship to heme oxygenase-1. J Neurochem. 2009;110(4):1241-1253.
[218]
HeverinM, Bogdanovic N, LtjohannD, BayerT, Bjrkhem I. Changes in the levels of cerebral and extracerebral sterols in the brain of patients with Alzheimer's disease. J Lipid Res. 2004;45(1):186.
[219]
Korologou-LindenR, Bhatta L, BrumptonBM, et al. The causes and consequences of Alzheimer's disease: phenome-wide evidence from Mendelian randomization. Nat Commun. 2022;13(1):4726.
[220]
GuerreiroRJ, Gustafson DR, HardyJ. The genetic architecture of Alzheimer's disease: beyond APP, PSENs and APOE. Neurobiol Aging. 2012;33(3):437-456.
[221]
HoltzmanDM, HerzJ, BuG. Apolipoprotein e and apolipoprotein e receptors: normal biology and roles in Alzheimer disease. Cold Spring Harbor Perspect Med. 2012;2(3):a6312.
[222]
MahleyRW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science. 1988;240(4852):622-630.
[223]
KimJ, BasakJM, HoltzmanDM. The role of apolipoprotein E in Alzheimer's disease. Neuron. 2009;63(3):287-303.
[224]
Serrano-PozoA, DasS, HymanBT. APOE and Alzheimer's disease: advances in genetics, pathophysiology, and therapeutic approaches. Lancet Neurol. 2021;20(1):68-80.
[225]
TachibanaM, HolmML, LiuCC, Shinohara M, KanekiyoT. APOE4-mediated amyloid-beta pathology depends on its neuronal receptor LRP1. J Clin Invest. 2019;129(89).
[226]
CastellanoJM, KimJ, StewartFR, et al. Human apoE isoforms differentially regulate brain amyloid-beta peptide clearance. Sci Transl Med. 2011;3(89):57r-89r.
[227]
VerghesePB, Castellano JM, GaraiK, et al. ApoE influences amyloid-β (Aβ) clearance despite minimal apoE/Aβ association in physiological conditions. Proc Natl Acad Sci USA. 2013;110(19):E1807-E1816.
[228]
BasakJM, Verghese PB, YoonH, KimJ, Holtzman DM. Low-density lipoprotein receptor represents an apolipoprotein E-independent pathway of a uptake and degradation by astrocytes. J Biol Chem. 2012;287(17):13959-13971.
[229]
KanekiyoT, ZhangJ, LiuQ, LiuCC, BuG. Heparan sulphate proteoglycan and the low-density lipoprotein receptor-related protein 1 constitute major pathways for neuronal amyloid-uptake. J Neurosci. 2011;31(5):1644-1651.
[230]
SagareA, DeaneR, BellRD, et al. Clearance of amyloid-beta by circulating lipoprotein receptors. Nat Med. 2007;13(9):1029-1031.
[231]
CastellanoJM, DeaneR, GottesdienerAJ, et al. Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood clearance in a mouse model of-amyloidosis. Proc Natl Acad Sci USA. 2012;109(38):15502.
[232]
DeaneR, SagareA, ZlokovicBV. The role of the cell surface LRP and soluble LRP in blood-brain barrier Abeta clearance in Alzheimer's disease. Curr Pharm Des. 2008;14(16):1601-1605.
[233]
BalesKR, VerinaT, DodelRC, et al. Lack of apolipoprotein E dramatically reduces amyloid |[beta]|-peptide deposition. Nat Genet. 1997;17(3):263-264.
[234]
FryerJD. Human apolipoprotein e4 alters the amyloid-? 40:42 ratio and promotes the formation of cerebral amyloid angiopathy in an amyloid precursor protein transgenic model. J Neurosci. 2005;25(11):2803-2810.
[235]
HoltzmanDM. Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease. Proc Natl Acad Sci USA. 2000;97(6):2892-2897.
[236]
FaganAM, WatsonM, ParsadanianM, BalesKR, Holtzman DM. Human and murine ApoE markedly alters a beta metabolism before and after plaque formation in a mouse model of Alzheimer's disease. Neurobiol Dis. 2002;9(3):305-318.
[237]
ShadlenMF. Effects of age and ethnicity on the link between APOE4 and Alzheimer disease. JAMA. 1998;279(8).
[238]
CorderEH, Saunders AM, StrittmatterWJ, SchmechelDE, Pericak-Vance MA. Gene dose of Apolipoprotein E type 4 allele and the risk of Alzheimers disease in late onset families. Science. 1993;8(5123):41-43.
[239]
SaundersAM, Strittmatter WJ, SchmechelD, et al. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology. 1993;43(8):1467-1472.
[240]
RosesAD. Apolipoprotein E alleles as risk factors in Alzheimer's disease. Annu Rev Med. 1996;47(1):387-400.
[241]
MahleyRW, HuangY, RallSC. Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia): questions, quandaries, and paradoxes. J Lipid Res. 1999;40(11):1933-1949.
[242]
LiuCC, Kanekiyo T, XuH, BuG. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013;9(2):106-118.
[243]
StrittmatterWJ, Weisgraber KH, HuangDY, et al. Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease. Proc Natl Acad Sci USA. 1993;90(17):8098-8102.
[244]
LefterovI, WolfeCM, FitzNF, Nam KN, KoldamovaR. APOE2 orchestrated differences in transcriptomic and lipidomic profiles of postmortem AD brain. Alzheimer's Res Ther. 2019;11(1).
[245]
JuvaK, Verkkoniemi A, ViramoP, et al. Apolipoprotein e, cognitive function, and dementia in a general population aged 85 years and over. Int Psychogeriatr. 2000;12(3):379-387.
[246]
O'DonoghueMC, MurphySE, ZamboniG, Nobre AC, MackayCE. APOE genotype and cognition in healthy individuals at risk of Alzheimer's disease: a review. Cortex. 2018:S1641630852.
[247]
TrachtenbergAJ, Filippini N, CheesemanJ, et al. The effects of APOE on brain activity do not simply reflect the risk of Alzheimer's disease. Neurobiol Aging. 2012;33(3):618.e1-618.e13.
[248]
BoisvertMM, Erikson GA, ShokhirevMN, AllenNJ. The aging astrocyte transcriptome from multiple regions of the mouse brain. Cell Rep. 2018;22(1):269-285.
[249]
ZamanianJL, XuL, FooLC, Nouri N, BarresBA. Genomic analysis of reactive astrogliosis. J Neurosci. 2012;32(18):6391-6410.
[250]
ZhaoN, RenY, YamazakiY, et al. Alzheimer's risk factors age, APOE genotype, and sex drive distinct molecular pathways. Neuron. 2020;106(5):727-742.
CrossRef Google scholar
[251]
DulewiczM, Kulczyska-Przybik A, SowikA, BorawskaR, Mroczko B. Fatty acid binding protein 3 (FABP3) and apolipoprotein e4 (ApoE4) as lipid Metabolism-Related biomarkers of Alzheimer's disease. J Clin Med. 2021;10(14).
[252]
RawatV, WangS, JianS, Bar R, YassineHN. ApoE4 alters ABCA1 membrane trafficking in astrocytes. J Neurosci. 2019;39(48):9611-9622.
[253]
QiaoF, GaoXP, YuanL, Cai HY, QiJS. Apolipoprotein e4 impairs in vivo hippocampal Long-Term synaptic plasticity by reducing the phosphorylation of CaMKII and CREB. J Alzheimers Dis. 2014;41(4):1165.
[254]
RodriguezGA, BurnsMP, WeeberEJ, Rebeck GW. Young APOE4 targeted replacement mice exhibit poor spatial learning and memory, with reduced dendritic spine density in the medial entorhinal cortex. Learn Mem. 2013;20(5):256-266.
[255]
TerrisseL, Poirier J, BertrandP, MerchedA, Rassart E. Increased levels of apolipoprotein d in cerebrospinal fluid and hippocampus of alzheimer's patients. J Neurochem. 1998;71(4):1643-1650.
[256]
LinYT, SeoJ, GaoF, et al. APOE4 causes widespread molecular and cellular alterations associated with alzheimer's disease phenotypes in human iPSC-Derived brain cell types - ScienceDirect. Neuron. 2018;98(6).
[257]
SienskiG, Narayan P, BonnerJM, et al. APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia. Sci Transl Med. 13.
[258]
QiG, MiY, ShiX, GuH, BrintonRD, Yin F. ApoE4 impairs Neuron-Astrocyte coupling of fatty acid metabolism. Cell Rep. 2021;34(1):108572.
[259]
ZhangY, ChenK, SloanSA, et al. An RNA-Sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci. 2014;34(36):11929-11947.
[260]
WatkinsPA. Fatty acid activation. Prog Lipid Res. 1997;36(1):55-83.
[261]
UhlénM, Fagerberg L, HallströmBM, et al. Proteomics. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419.
[262]
EllisJM, FrahmJL, LiLO, Coleman RA. Acyl-coenzyme A synthetases in metabolic control. Curr Opin Lipidol. 2010;21(3):212-217.
[263]
SteinbergSJ, Morgenthaler J, HeinzerAK, SmithKD, Watkins PA. Very long-chain Acyl-CoA synthetases human “bubblegum” represents a new family of proteins capable of activating very long-chain fatty acids. J Biol Chem. 2000;275(45):35162-35169.
[264]
PeiZ, OeyNA, ZuidervaartMM, et al. The Acyl-CoA synthetase ∖“bubblegum∖” (Lipidosin): further characterization and role in neuronal fatty acid ?-Oxidation. J Biol Chem. 2003;278(47):47070-47078.
[265]
LiMD, BurnsTC, MorganAA, Khatri P. Integrated multi-cohort transcriptional meta-analysis of neurodegenerative diseases. Acta Neuropathol Com. 2014;2(1):93.
[266]
JunG, Ibrahim-Verbaas CA, VronskayaM, et al. A novel Alzheimer disease locus located near the gene encoding tau protein. Mol Psychiatry. 2016;21(1):108-117.
[267]
EllisJM, BowmanCE, WolfgangMJ. Metabolic and Tissue-Specific regulation of Acyl-CoA metabolism. PLoS One. 2015;10(3):e116587.
[268]
MarszalekJR, Kitidis C, DararutanaA, LodishHF. Acyl-CoA synthetase 2 overexpression enhances fatty acid internalization and neurite outgrowth. J Biol Chem. 2004;279(23):23882.
[269]
KlettEL, ChenS, YechoorA, Lih FB, ColemanRA. Long-chain acyl-CoA synthetase isoforms differ in preferences for eicosanoid species and long-chain fatty acids. J Lipid Res. 2017;58(5):884-894.
[270]
HornCGV, Caviglia JM, LiLO, WangS, Coleman RA. Characterization of recombinant long-chain rat acyl-CoA synthetase isoforms 3 and 6: identification of a novel variant of isoform 6. Biochemistry. 2005;44(5):1635-1642.
[271]
KimHC, LeeSW, ChoYY, Lim JM, RyooZY, LeeEJ. RNA interference of long-chain acyl-CoA synthetase 6 suppresses the neurite outgrowth of mouse neuroblastoma NB41A3 cells. Mol Med Rep. 2009;2(4):669-674.
[272]
WangX, ZhuM, HjorthE, et al. Resolution of inflammation is altered in Alzheimer's disease. Alzheimers Dement. 2015;11(1):40-50.
[273]
FernandezRF, KimSQ, ZhaoY, Foguth RM, EllisJM. Acyl-CoA synthetase 6 enriches the neuroprotective omega-3 fatty acid DHA in the brain. Proc Natl Acad Sci USA. 2018;115(49):201807958.
[274]
Chouinard-WatkinsR, Bazinet RP ACSL6 is critical for maintaining brain DHA levels. Proc Natl Acad Sci USA. 115(49):12343-12345.
[275]
FernandezRF, Pereyra AS, DiazV, WilsonES, EllisJM. Acyl-CoA synthetase 6 is required for brain docosahexaenoic acid retention and neuroprotection during aging. JCI Insight. 2021;6(11).
[276]
FernandezRF, EllisJM. Acyl-CoA synthetases as regulators of brain phospholipid acyl-chain diversity. Prostaglandins Leukot Essent Fatty Acids. 2020;161:102175.
[277]
SharmaK, Schmitt S, BergnerCG, et al. Cell type-and brain region-resolved mouse brain proteome. Nat Neurosci. 2015;18(12):1819-1831.
[278]
AtlasAMB. Allen brain atlas. Neuron. 2009.
[279]
OrreM, Kamphuis W, OsbornLM, et al. Acute isolation and transcriptome characterization of cortical astrocytes and microglia from young and aged mice. Neurobiol Aging. 2014;35(1):1-14.
[280]
CahoyJD, EmeryB, KaushalA, et al. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci. 2008;28(1):264-278.
[281]
SoupeneE, Kuypers FA. Mammalian Long-Chain Acyl-CoA synthetases. Exp Biol Med. 2008;233(5):507-521.
[282]
HaleBJ, Fernandez RF, KimSQ, et al. Acyl-CoA synthetase 6 enriches seminiferous tubules with the ω-3 fatty acid docosahexaenoic acid and is required for male fertility in the mouse. J Biol Chem. 2019;294(39):14394-14405.
[283]
SoupeneE, Kuypers FA. Multiple erythroid isoforms of human long-chain acyl-CoA synthetases are produced by switch of the fatty acid gate domains. BMC Mol Biol. 2006;7:21.
[284]
LeeEJ, KimHC, YongYC, Byun SJ, LimJM, RyooZY. Alternative promotion of the mouse acyl-CoA synthetase 6 (mAcsl6) gene mediates the expression of multiple transcripts with 5'-end heterogeneity: genetic organization of mAcsl6 variants. Biochem Biophys Res Commun. 2005;327(1):84-93.
[285]
MalhotraKT, Malhotra K, LubinBH, KuypersFA. Identification and molecular characterization of acyl-CoA synthetase in human erythrocytes and erythroid precursors. Biochem J. 344 Pt 1999;1(1):135.
[286]
SoupeneE, DinhNP, SiliakusM, Kuypers FA. Activity of the acyl-CoA synthetase ACSL6 isoforms: role of the fatty acid Gate-domains. BMC Biochem. 2010;11:18.
[287]
GilquinB, Taillebourg E, CherradiN, et al. The AAA+ ATPase ATAD3A controls mitochondrial dynamics at the interface of the inner and outer membranes. Mol Cell Biol. 2010;30(8):11.
[288]
DesaiR, Frazier AE, DurigonR, et al. ATAD3 gene cluster deletions cause cerebellar dysfunction associated with altered mitochondrial DNA and cholesterol metabolism. Brain. 2017;140(6):1595-1610.
[289]
ZhaoY, SunX, HuD, et al. ATAD3A oligomerization causes neurodegeneration by coupling mitochondrial fragmentation and bioenergetics defects. Nat Commun. 2019;10(1):1371.
[290]
HarelT, YoonWH, GaroneC, et al. Recurrent de novo and biallelic variation of ATAD3A, encoding a mitochondrial membrane protein, results in distinct neurological syndromes. Am J Hum Genet. 2016;99(4):831-845.
[291]
JanikiewiczJ, Szymański J, MalinskaD, et al. Mitochondria-associated membranes in aging and senescence: structure, function, and dynamics. Cell Death Dis. 2018;9(3).
CrossRef Google scholar
[292]
HayashiT, Rizzuto R, HajnoczkyG, SuTP. MAM: more than just a housekeeper. Trends Cell Biol. 2009;19(2):81-88.
[293]
RusiolAE, CuiZ, ChenMH, Vance JE. A unique mitochondria-associated membrane fraction from rat liver has a high capacity for lipid synthesis and contains pre-Golgi secretory proteins including nascent lipoproteins. J Biol Chem. 1994;269(44):27494-27502.
[294]
VanceJE. Molecular and cell biology of phosphatidylserine and phosphatidylethanolamine metabolism. Prog Nucleic Acid Res Mol Biol. 2003;75:69-111.
[295]
TagayaM, Arasaki K. Regulation of mitochondrial dynamics and autophagy by the mitochondria-associated membrane. Adv Exp Med Biol. 2017;997:33-47.
[296]
CsordsG, VrnaiP, GolenrT, Roy S, HajnczkyG. Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface. Mol Cell. 2010;39(1):121-132.
[297]
ZhaoY, HuD, WangR, et al. ATAD3A oligomerization promotes neuropathology and cognitive deficits in Alzheimer's disease models. Nat Commun. 2022;13(1):1121.
[298]
DjeltiF, Braudeau J, HudryE, et al. CYP46A1 inhibition, brain cholesterol accumulation and neurodegeneration pave the way for Alzheimer's disease. Brain. 2015;138(Pt 8):2383-2398.
[299]
MontesinosJ, PeraM, LarreaD, et al. The Alzheimer's disease-associated C99 fragment of APP regulates cellular cholesterol trafficking. EMBO J. 2020;39(20):e103791.
[300]
WeigelD, JackleH. The fork head domain: a novel DNA binding motif of eukaryotic transcription factors? Cell. 1990;63(3):455-456.
[301]
FlachsbartF, Caliebe A, KleindorpR, et al. Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc Natl Acad Sci USA. 2009;106(8):2700-2705.
[302]
WillcoxBJ, Portion TA, HeQ, et al. FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci USA. 2008;105(37):13987-13992.
[303]
ShimokawaI, Komatsu T, HayashiN, et al. The life-extending effect of dietary restriction requires Foxo3 in mice. Aging Cell. 2015;14(4):707-709.
[304]
ChiacchieraF, SimoneC. The AMPK-FoxO3A axis as a target for cancer treatment. Cell cycle (Georgetown, Tex). 2010;9(6):1091-1096.
[305]
ArmandoV, Burgering B. Stressing the role of FoxO proteins in lifespan and disease. Nat Rev Mol Cell Biol. 2007;8(6):440-450.
[306]
BeekmanM, Nederstigt C, SuchimanH, et al. Genome-wide association study (GWAS)-identified disease risk alleles do not compromise human longevity. Proc Natl Acad Sci USA. 2010;107(42).
[307]
ZettergrenA, KernS, Ryd茅nL, et al. Genetic variation in FOXO3 is associated with self-rated health in a population-based sample of older individuals. J Gerontol A Biol Med. 2018;73(11):1453.
[308]
SoerensenM, Nygaard M, DatoS, StevnsnerT, Christiansen L. Association study of FOXO3A SNPs and aging phenotypes in Danish oldest-old individuals. Aging Cell. 2015;14(1):60-66.
[309]
PaikJ, DingZ, NarurkarR, et al. FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis. Cell Stem Cell. 2009;5(5):540-553.
CrossRef Google scholar
[310]
RenaultVM, Rafalski VA, MorganAA, et al. FoxO3 regulates neural stem cell homeostasis. Cell Stem Cell. 2009;5(5):540-553.
[311]
SchffnerI, Minakaki G, KhanMA, BaltaEA, LieDC. FoxO function is essential for maintenance of autophagic flux and neuronal morphogenesis in adult neurogenesis. Neuron. 2018;99(6).
[312]
YeoH, Lyssiotis CA, ZhangY, et al. FoxO3 coordinates metabolic pathways to maintain redox balance in neural stem cells. EMBO J. 2014;32(19):2589-2602.
[313]
Caballero-CaballeroA, Engel T, Martinez-VillarrealJ, et al. Mitochondrial localization of the forkhead box class O transcription factor FOXO3a in brain. J Neurochem. 2013;124(6):749-756.
[314]
LehtinenMK, YuanZ, BoagPR, et al. A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell. 2006;125(5):987.
[315]
SriramK. Deficiency of TNF receptors suppresses microglial activation and alters the susceptibility of brain regions to MPTP-induced neurotoxicity: role of TNF- Faseb J. 2006;20(6):670-682.
[316]
WoiciechowskyC, Sch枚ning B, Stoltenburg-DidingerG, StockhammerF, VolkHD. Brain-IL-1 beta triggers astrogliosis through induction of IL-6: inhibition by propranolol and IL-10. Med Sci Monit. 2004;10(9):325-330.
[317]
BuffoA, Rolando C, CerutiS. Astrocytes in the damaged brain: molecular and cellular insights into their reactive response and healing potential. Biochem Pharmacol. 2010;79(2):77-89.
[318]
CuiM, HuangY, TianC, Zhao Y, ZhengJ. FOXO3a inhibits TNF-α-and IL-1β-induced astrocyte proliferation: implication for reactive astrogliosis. Glia. 2011;59(4):641-654.
[319]
DuS, JinF, ManeixL, et al. FoxO3 deficiency in cortical astrocytes leads to impaired lipid metabolism and aggravated amyloid pathology. Aging Cell. 2021;20(8):e13432.
[320]
NguyenTB, LouieSM, DanieleJR, et al. DGAT1-dependent lipid droplet biogenesis protects mitochondrial function during starvation-induced autophagy. Dev Cell. 2017;42(1):9-21.
[321]
EhehaltR, KellerP, HaassC, Thiele C, SimonsK. Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts. J Cell Biol. 2003;160(1):113-123.
[322]
SaidoT, Leissring MA. Proteolytic degradation of amyloid beta-Protein. Cold Spring Harbor Perspect Med. 2012;2(6):a6379.
[323]
HeG, LuoW, LiP, et al. Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease. Nature. 2010;467(7311):95-98.
[324]
ChuJ, LiJG, JoshiYB, et al. Gamma Secretase-Activating protein is a substrate for caspase-3: implications for alzheimer's disease. Biol Psychiat. 2015;77(8):720-728.
[325]
PerezSE, NadeemM, Malek-AhmadiMH, HeB, MufsonEJ. Frontal cortex and hippocampal-secretase activating protein levels in prodromal alzheimer disease. Neurodegener Dis. 2017:235-241.
[326]
SatohJ, Tabunoki H, IshidaT, SaitoY, ArimaK. Immunohistochemical characterization of secretase activating protein expression in Alzheimer's disease brains. Neuropathol Appl Neurobiol. 2012;38(2):132-141.
[327]
FloudasCS, UmN, KambohM, Barmada MM, VisweswaranS. Identifying genetic interactions associated with late-onset Alzheimer's disease. Biodata Min. 2014;7(1):35.
[328]
ZhuM, TaoY, HeQ, et al. A common GSAP promoter variant contributes to Alzheimer's disease liability. Neurobiol Aging. 2014;35(11):2651-2656.
[329]
XuP, ChangJC, ZhouX, Wang W, Greengard P GSAP regulates lipid homeostasis and mitochondrial function associated with Alzheimer's disease. J Exp Med. 218(8):e20202446.
[330]
ChuJ, Lauretti E, CraigeCP, PraticòD. Pharmacological modulation of GSAP reduces amyloid-β levels and tau phosphorylation in a mouse model of Alzheimer's disease with plaques and tangles. J Alzheimers Dis. 2014;41(3):729-737.
[331]
PeraM, LarreaD, Guardia-LaguartaC, et al. Increased localization of APP-C99 in mitochondria-associated ER membranes causes mitochondrial dysfunction in Alzheimer disease. EMBO J. 2017;36(22):3356-3371.
[332]
PreteDD, SuskiJM, OulsB, et al. Localization and processing of the amyloid-beta protein precursor in mitochondria-associated membranes. J Alzheimers Dis. 2016;55(4):1549-1570.
[333]
Area-GomezE, MariaDCLC, TambiniMD, et al. Upregulated function of mitochondria-associated ER membranes in Alzheimer disease. EMBO J. 2012;31(21):4106-4123.
[334]
HedskogL, PinhoCM, FiladiR, et al. Modulation of the endoplasmic reticulum-mitochondria interface in Alzheimer's disease and related models. Proc Natl Acad Sci USA. 2013;110(19):7916-7921.
[335]
Martino AdamiPV, Nichtová Z, WeaverDB, et al. Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease. J Cell Sci. 2019;132(20):jcs229906.
[336]
KosicekM, Hecimovic S. Phospholipids and alzheimer's disease: alterations, mechanisms and potential biomarkers. Int J Mol Sci. 2013;14(1):1310-1322.
[337]
CorderEH, Saunders AM, StrittmatterWJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993;261(5123):921-923.
[338]
MartinsIJ, HoneE, FosterJK, et al. Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease. Mol Psychiatry. 2006;11(8):721-736.
[339]
EckertGP, RennerK, EckertSH, et al. Mitochondrial dysfunction–a pharmacological target in Alzheimer's disease. Mol Neurobiol. 2012;46(1):136-150.
[340]
GatzM, Reynolds CA, FratiglioniL, et al. Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry. 2006;63(2):168-174.
[341]
BellRD, Zlokovic BV. Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer's disease. Acta Neuropathol. 2009;118(1):103-113.
[342]
ReitzC, MayeuxR. Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem Pharmacol. 2014;88(4):640-651.
[343]
AisenPS, Cummings J, JackCR, et al. On the path to 2025: understanding the Alzheimer's disease continuum. Alzheimers Res Ther. 2017;9(1):60.
[344]
CummingsJL, Morstorf T, ZhongK. Alzheimer's disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res Ther. 2014;6(4):37.
[345]
HampelH, FrankR, BroichK, et al. Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives. Nat Rev Drug Discov. 2010;9(7):560-574.
[346]
GoldeTE, Schneider LS, KooEH. Anti-aβ therapeutics in Alzheimer's disease: the need for a paradigm shift. Neuron. 2011;69(2):203-213.
[347]
De StrooperB, KarranE. The cellular phase of Alzheimer's disease. Cell. 2016;164(4):603-615.
[348]
GoodenbergerM, Jenkins RB. Genetics of adult glioma. Cancer Genet. 2012;205(12).
[349]
VenurVA, Peereboom DM, AhluwaliaMS. Current medical treatment of glioblastoma. Cancer Treat Res. 2015;163:103-115.
[350]
JooK, KimJ, JinJ, et al. Patient-Specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ. Cell Rep. 2013;3(1).
[351]
RicardD, IdbaihA, DucrayF, Lahutte M, HoangxuanK, DelattreJY. Primary brain tumours in adults. Lancet. 2012;379(9830):1984-1996.
[352]
LibbyCJ, TranAN, ScottSE, Griguer C, HjelmelandAB. The pro-tumorigenic effects of metabolic alterations in glioblastoma including brain tumor initiating cells. Biochim Biophys Acta. 2018;1869(2):175-188.
[353]
AgnihotriS, ZadehG. Metabolic reprogramming in glioblastoma: the influence of cancer metabolism on epigenetics and unanswered questions. Neuro Oncol. 2016;18(2):160-172.
[354]
IntlekoferAM, FinleyLWS. Metabolic signatures of cancer cells and stem cells. Nat Metab. 2019;1(2):177-188.
[355]
HanahanD, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674.
[356]
López-LázaroM. The warburg effect: why and how do cancer cells activate glycolysis in the presence of oxygen? Anticancer Agents Med Chem. 2008;8(3):305-312.
[357]
DurajT, Garcromero N, CarrinavarroJ, et al. Beyond the warburg effect: oxidative and glycolytic phenotypes coexist within the metabolic heterogeneity of glioblastoma. Cells-Basel. 10(2):202.
[358]
HoangnhLB, Siebzehnrubl FA, YangC, TanoSS, Deleyrolle LP. Infiltrative and drug鈥 恟esistant slowcling cells support metabolic heterogeneity in glioblastoma. EMBO J. 2018;37(23):e98772.
[359]
DumanC, YaqubiK, HoffmannA, et al. Acyl-CoA-binding protein drives glioblastoma tumorigenesis by sustaining fatty acid oxidation. Cell Metab. 2019;30(2):274-289.
[360]
AntonellaDR, SerenaP, MarcoR, et al. A radial glia gene marker, fatty acid binding protein 7 (FABP7), is involved in proliferation and invasion of glioblastoma cells. PLoS One. 2012;7(12):e52113.
[361]
GuptaK, Vuckovic I, ZhangS, et al. Radiation induced metabolic alterations associate with tumor aggressiveness and poor outcome in glioblastoma. Front Oncol. 2020;10:535.
[362]
SonB, LeeS, KimH, KangH, YounBH. Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma. Oncogene. 2020;39(1):36-49.
[363]
HuaL, ShaanP, AffleckVS, et al. Fatty acid oxidation is required for the respiration and proliferation of malignant glioma cells. Neuro-oncol. 2017;19(1):43-54.
[364]
HannaVS, Ebtisam A. Synopsis of arachidonic acid metabolism: a review. J Adv Res. 2018:23-32.
[365]
Juric-SekharG, Zarkovic K, WaegG, CipakA, Zarkovic N. Distribution of 4-hydroxynonenal-protein conjugates as a marker of lipid peroxidation and parameter of malignancy in astrocytic and ependymal tumors of the brain. Tumori. 2009;95(6):762-768.
[366]
ZajdelA, Wilczok A, SlowinskiJ, OrchelJ, Mazurek U. Aldehydic lipid peroxidation products in human brain astrocytomas. J Neurooncol. 2007;84(2):167-173.
[367]
ZarkovicK, JuricG, WaegG, Kolenc D, ZarkovicN. Immunohistochemical appearance of HNE-protein conjugates in human astrocytomas. Biofactors. 2010;24(1-4):33-40.
[368]
Atilla-GokcumenGE, Muro E, Relat-GobernaJ, et al. Dividing cells regulate their lipid composition and localization. Cell. 2014;156(3):428-439.
[369]
LopezDH, Bestard-Escalas J, GarateJ, et al. Tissue-selective alteration of ethanolamine plasmalogen metabolism in dedifferentiated colon mucosa. Biochim Biophys Acta Mol Cell Biol Lipids. 2018;1863(8):928-938.
[370]
SangTL, LeeJC, KimJW, Cho SY, SeongJK, MoonMH. Global changes in lipid profiles of mouse cortex, hippocampus, and hypothalamus upon p53 knockout. Sci Rep. 2016;6:36510.
[371]
BaenkeF, PeckB, MiessH, Schulze A. Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development. Dis Model Mech. 2013;6(6):1353-1363.
[372]
GimpleRC, Kidwell RL, KimLJY, et al. Glioma Stem Cell-Specific Superenhancer Promotes Polyunsaturated Fatty-Acid Synthesis to Support EGFR Signaling. Cancer Discov. 2019;9(9):1248-1267.
[373]
ZouYK, Watters A, ChengN, PerryCE, ChenQ. Polyunsaturated fatty acids from astrocytes activate PPARγ signaling in cancer cells to promote brain metastasis. Cancer Discov. 2019;9(12):1720-1735.
[374]
ChengX, GengF, PanM, et al. Targeting DGAT1 ameliorates glioblastoma by increasing fat catabolism and oxidative stress. Cell Metab. 2020;32(2):229-242.
[375]
OmuroA, Deangelis LM. Glioblastoma and other malignant gliomas: a clinical review. J Am Med Assoc. 2013;310(17):1842-1850.
[376]
WenPY, KesariS. Malignant gliomas in adults. New Engl J Med. 2008;359(5):492-507.
[377]
AcciolyMT, Pacheco P, Maya-MonteiroCM, et al. Lipid bodies are reservoirs of cyclooxygenase-2 and sites of prostaglandin-E2 synthesis in colon cancer cells. Cancer Res. 2008;68(6):1732-1740.
[378]
DuW, ZhangL, Brett-MorrisA, et al. HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism. Nat Commun. 2017;8(1).
CrossRef Google scholar
[379]
GengF, ChengX, WuX, et al. Inhibition of SOAT1 suppresses glioblastoma growth via blocking SREBP-1-mediated lipogenesis. Clin Cancer Res. 2016;22(21):5337-5348.
[380]
GengF, GuoD. Lipid droplets, potential biomarker and metabolic target in glioblastoma. Intern Med Rev. 2017;3(5).
CrossRef Google scholar
[381]
MitraR, LeTT, GorjalaP, Goodman OB. Positive regulation of prostate cancer cell growth by lipid droplet forming and processing enzymes DGAT1 and ABHD5. BMC Cancer. 2017;17(1):631.
[382]
PucerA, BrglezV, PayrC, Pungerar J, PetanT. Group X secreted phospholipase A2 induces lipid droplet formation and prolongs breast cancer cell survival. Mol Cancer. 2013;12(1):111.
[383]
SevinskyCJ, FaizaK, LeilaK, Anza D, RaoMK, ConklinDS. NDRG1 regulates neutral lipid metabolism in breast cancer cells. Breast Cancer Res. 2018;20(1):55.
[384]
SunamiY, RebeloA, KleeffJ. Lipid metabolism and lipid droplets in pancreatic cancer and stellate cells. Cancers. 2017;10(1):3.
[385]
Tauchi-SatoK, OzekiS, HoujouT, Taguchi R, FujimotoT. The surface of lipid droplets is a phospholipid monolayer with a unique fatty acid composition. J Biol Chem. 2002;277(46):44507-44512.
[386]
JacksonCL. Lipid droplet biogenesis. Curr Opin Cell Biol. 2019;59:88-96.
[387]
OlzmannJA, Carvalho P. Dynamics and functions of lipid droplets. Nat Rev Mol Cell Biol. 2019;20(3):137-155.
[388]
PaarM, JungstC, SteinerNA, et al. Remodeling of lipid droplets during lipolysis and growth in adipocytes. J Biol Chem. 2012;287(14):11164-11173.
[389]
KlionskyDJ, EmrSD. Autophagy as a regulated pathway of cellular degradation. Science. 2000;290(5497):1717-1721.
[390]
MizushimaN, Komatsu M. Autophagy: renovation of cells and tissues. Cell. 2011;147(4):728-741.
[391]
MizushimaN, LevineB, CuervoAM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature. 2008;451(7182):1069.
[392]
SinghR, Kaushik S, WangY, et al. Autophagy regulates lipid metabolism. Nature. 2009;458(7242):1131-1135.
[393]
WuX, GengF, ChengX, et al. Lipid droplets maintain energy homeostasis and glioblastoma growth via autophagic release of stored fatty acids. iScience. 2020;23(10):101569.
[394]
GuoD, Reinitz F, YoussefM, et al. An LXR agonist promotes glioblastoma cell death through inhibition of an EGFR/AKT/SREBP-1/LDLR-dependent pathway. Cancer Discov. 2011;1(5):442-456.
[395]
BjorkhemI. Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol. 2004;24(5):806-815.
[396]
DietschyJM, TurleySD. Cholesterol metabolism in the brain. Curr Opin Lipidol. 2001;12(2):105-112.
[397]
HayashiH, Campenot RB, VanceDE, VanceJE. Glial lipoproteins stimulate axon growth of central nervous system neurons in compartmented cultures. J Biol Chem. 2004;279(14):14009-14015.
[398]
Karten,B. Expression of ABCG1, but not ABCA1, correlates with cholesterol release by cerebellar astroglia. J Biol Chem. 2006;281(7):4049-4057.
[399]
WahrleSE, JiangH, ParsadanianM, et al. ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE. J Biol Chem. 2004;279(39):40987-40993.
[400]
OrthM, Bellosta S. Cholesterol: its regulation and role in central nervous system disorders. Cholesterol. 2012;2012:292598.
[401]
JingC, ZhangX, KusumoH, Costa LG, GuizzettiM. Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis. Biochim Biophys. 2013;1831(2).
[402]
RepaJJ. Regulation of absorption and ABC1-Mediated efflux of cholesterol by RXR heterodimers. Science. 2000;289(5484):1524-1529.
[403]
VenkateswaranA, Laffitte BA, JosephSB, et al. Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha. Proc Natl Acad Sci USA. 2000;97(22):12097-12102.
[404]
ZelcerN, HongC, BoyadjianR, Tontonoz P. LXR regulates cholesterol uptake through Idol-Dependent ubiquitination of the LDL receptor. Science. 2009;325(5936):100-104.
[405]
VillaG, HulceJ, ZancaC, Bi J, MischelP. An LXR-Cholesterol axis creates a metabolic Co-Dependency for brain cancers. Cancer Cell. 2016;30(5):683-693.
[406]
FriedmanHS, KerbyT, CalvertH. Temozolomide and treatment of malignant glioma. Clin Cancer Res. 2000;6(7):2585-2597.
[407]
StuppR, MasonWP, VanD, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma - ScienceDirect. Cancer/Radiothrapie. 2005;9(3):196-197.
[408]
MassimoA, Valentina M, NicolettaL, et al. Exploring the link between ceramide and ionizing radiation. Glycoconjugate J. 2014;31(6-7):449-459.
[409]
BradyRO, KanferJN, MockMB, Fredrickson DS. The metabolism of sphingomyelin. II. Evidence of an enzymatic deficiency in Niemann-Pick diseae. Proc Natl Acad Sci USA. 1966;55(2):366-369.
[410]
Haimovitz-FriedmanA. Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J Exp Med. 1994;180(2):525-535.
[411]
SenchenkovA, LitvakDA, CabotMC. Targeting ceramide metabolism–a strategy for overcoming drug resistance. J Natl Cancer Inst. 2001;93(5):347-357.
[412]
MizushimaN, KoikeR, KohsakaH, et al. Ceramide induces apoptosis via CPP32 activation. FEBS Lett. 1996;395(2-3):267-271.
[413]
AbuhusainHJ, MatinA, QiaoQ, et al. A metabolic shift favoring sphingosine 1-Phosphate at the expense of ceramide controls glioblastoma angiogenesis. J Biol Chem. 2013;288(52):37355-37364.
[414]
Ji-SunJ, Young-Ho A, Byung-InM, Hee-SunK. Exogenous c2 ceramide suppresses matrix metalloproteinase gene expression by inhibiting ROS production and MAPK signaling pathways in PMA-Stimulated human astroglioma cells. Int J Mol Sci. 2016;17(4):477.
[415]
NgangaR, Oleinik N, OgretmenB. Mechanisms of ceramide-dependent cancer cell death. Adv Cancer Res. 2018;140:1-25.
[416]
GaultCR, ObeidLM, HannunYA. An overview of sphingolipid metabolism: from synthesis to breakdown. Adv Exp Med Biol. 2010;688:1-23.
[417]
BuehrerBM, BellRM. Inhibition of sphingosine kinase in vitro and in platelets. Implications for signal transduction pathways. J Biol Chem. 1992;267(5):3154-3159.
[418]
BrocklynJ, YoungN, RoofR. Sphingosine-1-phosphate stimulates motility and invasiveness of human glioblastoma multiforme cells. Cancer Lett. 2003;199(1):53-60.
[419]
BassiR, AnelliV, GiussaniP, Tettamanti G, VianiP, RiboniL. Sphingosine-1-phosphate is released by cerebellar astrocytes in response to bFGF and induces astrocyte proliferation through Gi-protein-coupled receptors. Glia. 2010;53(6):621-630.
[420]
AnelliV, GaultCR, ChengAB, Obeid LM. Sphingosine kinase 1 is up-regulated during hypoxia in U87MG glioma cells. J Biol Chem. 2008;283(6):3365-3375.
[421]
StrubGM, Maceyka M, HaitNC, MilstienS, Spiegel S. Extracellular and intracellular actions of sphingosine-1-phosphate. Adv Exp Med Biol. 2010;688:141-155.
[422]
CuvillierO, Pirianov G, KleuserB, VanekPG, Spiegel S. Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate. Nature. 1996;381(6585):800-803.
[423]
NagahashiM, AbeM, SakimuraK, Takabe K, WakaiT. The role of sphingosine-1-phosphate in inflammation and cancer progression. Cancer Sci. 2018;109(12):3671-3678.
[424]
MarfiaG, Campanella R, NavoneSE, et al. Autocrine/paracrine sphingosine-1-phosphate fuels proliferative and stemness qualities of glioblastoma stem cells. Glia. 2014;62(12):1968-1981.
[425]
ImDS, Clemens J, MacdonaldTL, LynchKR. Characterization of the human and mouse sphingosine 1-phosphate receptor, S1P5 (Edg-8): structure-activity relationship of sphingosine1-phosphate receptors. Biochemistry. 2001;40(46):14053-14060.
[426]
HlaT, MaciagT. An abundant transcript induced in differentiating human endothelial cells encodes a polypeptide with structural similarities to G-protein-coupled receptors. J Biol Chem. 1990;265(16):9308-9313.
[427]
MasanaMI, BrownRC, PuH, GurneyME, DubocovichML. Cloning and characterization of a new member of the G-protein coupled receptor EDG family. Recept Channels. 1995;3(4):255-262.
[428]
ZondagGC, PostmaFR, EttenIV, Verlaan I, MoolenaarWH. Sphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1. Biochem J. 330(Pt 2):605-609.
[429]
SiehlerS, Manning DR. Pathways of transduction engaged by sphingosine 1-phosphate through G protein-coupled receptors. Biochim Biophys Acta. 2002;1582(1-3):94-99.
[430]
SanchezT, HlaT. Structural and functional characteristics of S1P receptors. J Cell Biochem. 2004;92(5):913-922.
[431]
Bien-MöllerS, Lange S, HolmT, et al. Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme. Oncotarget. 2016;7(11):13031-13046.
[432]
YoshidaY, NakadaM, SugimotoN, et al. Sphingosine-1-phosphate receptor type 1 regulates glioma cell proliferation and correlates with patient survival. Int J Cancer. 2010;126(10):2341-2352.
[433]
BernhartE, DammS, WinterspergerA, et al. Interference with distinct steps of sphingolipid synthesis and signaling attenuates proliferation of U87MG glioma cells. Biochem Pharmacol. 2015;96(2):119-130.
[434]
YoungN, Brocklyn JRV. Roles of Sphingosine-1-Phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P2 on cell migration and invasiveness. Exp Cell Res. 2007;313(8):1615-1627.
[435]
LepleyD. The g protein鈥 揅oupled receptor S1P2 regulates Rho/Rho kinase pathway to inhibit tumor cell migration. Cancer Res. 2005;65(9):3788.
[436]
MalchinkhuuE, SatoK, MaehamaT, et al. S1P(2) receptors mediate inhibition of glioma cell migration through Rho signaling pathways independent of PTEN. Biochem Biophys Res Commun. 2008;366(4):963-968.
[437]
QuintK, StielN, NeureiterD, et al. The role of sphingosine kinase isoforms and receptors S1P1, S1P2, S1P3, and S1P5 in primary, secondary, and recurrent glioblastomas. Tumour Biol. 2014;35(9):8979-8989.
[438]
RothhammerV, Kenison JE, TjonE, et al. Sphingosine 1-phosphate receptor modulation suppresses pathogenic astrocyte activation and chronic progressive CNS inflammation. Proc Natl Acad Sci USA. 2017;114(8):201615413.
[439]
O'SullivanSA, O'Sullivan C, HealyLM, DevKK, Sheridan GK. Sphingosine 1-phosphate receptors regulate TLR4-induced CXCL5 release from astrocytes and microglia. J Neurochem. 2018;144(6):736-747.
[440]
QiY, ZhaoW, LiM, et al. High C-X-C motif chemokine 5 expression is associated with malignant phenotypes of prostate cancer cells via autocrine and paracrine pathways. Int J Oncol. 2018;53(1):358-370.
[441]
WindhRT, LeeMJ, HlaT, AnS, BarrAJ, Manning DR. Differential coupling of the sphingosine 1-Phosphate receptors edg-1, edg-3, and H218/Edg-5 to the gi, gq, and g12 families of heterotrimeric g proteins. J Biol Chem. 1999;274(39):27351-27358.
[442]
LiuY, WangX, LiJ, et al. Sphingosine 1-phosphate liposomes for targeted nitric oxide delivery to mediate anticancer effects against brain glioma tumors. Adv Mater. 2021;33(30):e2101701.
[443]
Bien-MöllerS, Lange S, HolmT, et al. Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme. Oncotarget. 15;2016;7(11):13031-13046.
[444]
RekersNH, SminiaP, PetersGJ. Towards tailored therapy of glioblastoma multiforme. J Chemother. 2011;23(4):187-199.
[445]
BryanL, PaughBS, KapitonovD, et al. Sphingosine-1-phosphate and interleukin-1 independently regulate plasminogen activator inhibitor-1 and urokinase-type plasminogen activator receptor expression in glioblastoma cells: implications for invasiveness. Mol Cancer Res. 2008;6(9):1469.
[446]
YoungN, Brocklyn JRV. Roles of Sphingosine-1-Phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P2 on cell migration and invasiveness. Exp Cell Res. 2007;313(8):1615-1627.
[447]
SatoK, TomuraH, IgarashiY, Ui M, OkajimaF. Possible involvement of cell surface receptors in sphingosine 1-phosphate-induced activation of extracellular signal-regulated kinase in C6 glioma cells. Mol Pharmacol. 1999;55(1):126-133.
[448]
MalchinkhuuE, SatoK, HoriuchiY, et al. Role of p38 mitogen-activated kinase and c-Jun terminal kinase in migration response to lysophosphatidic acid and sphingosine-1-phosphate in glioma cells. Oncogene. 2005;24(44):6676-6688.
[449]
BrocklynJRV, YoungN, RoofR. Sphingosine-1-phosphate stimulates motility and invasiveness of human glioblastoma multiforme cells. Cancer Lett. 2003;199(1):53-60.
[450]
YoshidaY, NakadaM, HaradaT, et al. The expression level of sphingosine-1-phosphate receptor type 1 is related to MIB-1 labeling index and predicts survival of glioblastoma patients. J Neuro-Oncol. 2010;98(1):41-47.
[451]
YoshidaY, NakadaM, SugimotoN, et al. Sphingosine-1-phosphate receptor type 1 regulates glioma cell proliferation and correlates with patient survival. Int J Cancer. 2010;126(10):2341-2352.
[452]
ShimizuF, Watanabe TK, ShinomiyaH, NakamuraY, Fujiwara T. Isolation and expression of a cDNA for human brain fatty acid-binding protein (B-FABP). Biochim Biophys Acta. 1997;1354(1):24-28.
[453]
XuLZ, Sanchez R, SaliA, HeintzN. Ligand specificity of brain lipid-binding protein. J Biol Chem. 1996;271(40):24711.
[454]
KurtzA, ZimmerA, SchngenF, Brning G, MillerT. The expression pattern of a novel gene encoding brain-fatty acid binding protein correlates with neuronal and glial cell development. Development. 1994;120(9):2637-2649.
[455]
OwadaY, Yoshimoto T, KondoH. Spatio-temporally differential expression of genes for three members of fatty acid binding proteins in developing and mature rat brains. J Chem Neuroanat. 1996;12(2):113-122.
[456]
Neural stem cell specific fluorescent chemical probe binding to FABP7. Proc Natl Acad Sci USA. 2012;109(26):10214-10217.
[457]
SinghSK, ClarkeID, TerasakiM, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63(18):5821.
[458]
LlagunoSA, ChenJ, ParadaLF. Signaling in malignant astrocytomas: role of neural stem cells and its therapeutic implications. Clin Cancer Res. 2009;15(23):7124-7129.
[459]
KaloshiG, Mokhtari K, CarpentierC, et al. FABP7 expression in glioblastomas: relation to prognosis, invasion and EGFR status. J Neurooncol. 2007;84(3):245-248.
[460]
AntonellaDR, SerenaP, MarcoR, et al. A radial glia gene marker, fatty acid binding protein 7 (FABP7), is involved in proliferation and invasion of glioblastoma cells. PLoS One. 2012;7(12):e52113.
[461]
MitaR, Beaulieu MJ, FieldC, GodboutR. Brain fatty acid-binding protein and omega-3/omega-6 fatty acids: mechanistic insight into malignant glioma cell migration. J Biol Chem. 2010;285(47):37005-37015.
[462]
MitaR, ColesJE, GlubrechtDD, Sung R, SunX, GodboutR. B-FABP-expressing radial glial cells: the malignant glioma cell of origin? Neoplasia. 2007;9(9):734-744.
[463]
LiangY, DiehnM, WatsonN, et al. Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme. Proc Natl Acad Sci USA. 2005;102(16):5814-5819.
[464]
LiangY, BollenAW, AldapeKD, Gupta N. Nuclear FABP7 immunoreactivity is preferentially expressed in infiltrative glioma and is associated with poor prognosis in EGFR-overexpressing glioblastoma. BMC Cancer. 2006;6(1):97.
[465]
BensaadK, FavaroE, LewisCA, et al. Fatty acid uptake and lipid storage induced by HIF-1 contribute to cell growth and survival after hypoxia-reoxygenation. Cell Rep. 2014;9(1):349-365.
[466]
HoangnhLB, Siebzehnrubl FA, YangC, TanoSS, Deleyrolle LP. Infiltrative and drug resistant slowcling cells support metabolic heterogeneity in glioblastoma. EMBO J. 2018;37(23):e98772.
[467]
XuX, WangY, ChoiWS, Sun X, GodboutR. Super resolution microscopy reveals DHA-dependent alterations in glioblastoma membrane remodelling and cell migration. Nanoscale. 2021;13(21):9706-9722.
[468]
PatonCM, NtambiJM. Biochemical and physiological function of stearoyl-CoA desaturase. Am J Physiol. 2008;297:E28-E37.
[469]
FlowersMT, NtambiJM. Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism. Curr Opin Lipidol. 2008;19(3):248-256.
[470]
WuX, ZouX, ChangQ, et al. The evolutionary pattern and the regulation of stearoyl-CoA desaturase genes. Biomed Res Int. 2013;2013:856521.
[471]
EckerJ, Liebisch G, GrandlM, SchmitzG. Lower SCD expression in dendritic cells compared to macrophages leads to membrane lipids with less mono-unsaturated fatty acids. Immunobiology. 2010;215(9-10):748-755.
[472]
ZhangL, GeL, ParimooS, Stenn K, ProutySM. Human stearoyl-CoA desaturase: alternative transcripts generated from a single gene by usage of tandem polyadenylation sites. Biochem J. 1999;340(Pt 1)(1):255-264.
[473]
NoushmehrH, Weisenberger DJ, DiefesK, et al. Cancer Genome Atlas Research Network. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010;17(5):510-522.
[474]
MenendezJA, LupuR. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer. 2007;7(10):763-777.
[475]
PeckB, Schulze A. Lipid desaturation - the next step in targeting lipogenesis in cancer? Febs J. 2016;283(15):2767-2778.
[476]
HilvoM, Denkert C, LehtinenL, et al. Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression. Cancer Res. 2011;71(9):3236-3245.
[477]
ScagliaN, Caviglia JM, IgalRA. High stearoyl-CoA desaturase protein and activity levels in simian virus 40 transformed-human lung fibroblasts. Biochim Biophys Acta. 2005;1687(1-3):141-151.
[478]
BrennanCW, Verhaak RG, McKennaA, et al. TCGA Research Network. The somatic genomic landscape of glioblastoma. Cell. 2013;155(2):462-477.
[479]
OatmanN, Dasgupta N, AroraP, ChoiK, Dasgupta B. Mechanisms of stearoyl CoA desaturase inhibitor sensitivity and acquired resistance in cancer. Sci Adv. 2021;7(7):d7459.

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