REFERENCES
1. Steinmetz JD, Seeher KM, Schiess N, et al. Global, regional, and national burden of disorders affecting the nervous system, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol. 2024;23:344-81.
2. Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443:787-95.
3. Woldetsadik AD, Vogel MC, Rabeh WM, Magzoub M. Hexokinase II-derived cell‐penetrating peptide targets mitochondria and triggers apoptosis in cancer cells. FASEB J. 2017;31:2168-84.
4. Martínez-reyes I, Chandel NS. Mitochondrial TCA cycle metabolites control physiology and disease. Nat Commun. 2020;11:102.
5. Olivas-Aguirre M, Torres-López L, Valle-Reyes JS, Hernández-Cruz A, Pottosin I, Dobrovinskaya O. Cannabidiol directly targets mitochondria and disturbs calcium homeostasis in acute lymphoblastic leukemia. Cell Death Dis. 2019;10:779.
6. Park A, Kim K, Park I, et al. Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice. Nat Commun. 2023;14:3746.
7. Fang W, Jiang L, Zhu Y, et al. Methionine restriction constrains lipoylation and activates mitochondria for nitrogenic synthesis of amino acids. Nat Commun. 2023;14:2504.
8. Zhou Y, Wei J, Deng G, et al. Delivery of low-density lipoprotein from endocytic carriers to mitochondria supports steroidogenesis. Nat Cell Biol. 2023;25:937-49.
9. Tripathi K, Ben-shachar D. Mitochondria in the central nervous system in health and disease: the puzzle of the therapeutic potential of mitochondrial transplantation. Cells. 2024;13:410.
10. Gyanwali B, Lim ZX, Soh J, et al. Alpha-Ketoglutarate dietary supplementation to improve health in humans. Trends Endocrinol Metab. 2022;33:136-46.
11. Liu L, Zhang W, Liu T, et al. The physiological metabolite α-ketoglutarate ameliorates osteoarthritis by regulating mitophagy and oxidative stress. Redox Biol. 2023;62:102663.
12. Asadi Shahmirzadi A, Edgar D, Liao C, et al. Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice. Cell Metab. 2020;32:447-56.e6.
13. Si X, Song Z, Liu N, Jia H, Liu H, Wu Z. α-Ketoglutarate restores intestinal barrier function through promoting intestinal stem cells-mediated epithelial regeneration in colitis. J Agric Food Chem. 2022;70:13882-92.
14. Sandalova E, Goh J, Lim ZX, et al. Alpha-ketoglutarate supplementation and BiologicaL agE in middle-aged adults (ABLE)—intervention study protocol. GeroScience. 2023;45:2897-907.
15. Filip R, Pierzynowski SG. The absorption, tissue distribution and excretion of enteraly administered α‐ketoglutarate in rats. J Anim Physiol Anim Nutr. 2007;92:182-9.
16. Lambert BD, Stoll B, Niinikoski H, Burrin DG, Pierzynowski S. Net portal absorption of enterally fed α-ketoglutarate is limited in young pigs. J Nutr. 2002;132:3383-6.
17. Hansen GE, Gibson GE. The α-ketoglutarate dehydrogenase complex as a Hub of plasticity in neurodegeneration and regeneration. Int J Mol Sci. 2022;23:12403.
18. Zaganas I, Spanaki C, Plaitakis A. Expression of human GLUD2 glutamate dehydrogenase in human tissues: Functional implications. Neurochem Int. 2012;61:455-62.
19. Plaitakis A, Kalef-Ezra E, Kotzamani D, Zaganas I, Spanaki C. The glutamate dehydrogenase pathway and its roles in cell and tissue biology in health and disease. Biology. 2017;6:11.
20. Herrero-Yraola A. Regulation of glutamate dehydrogenase by reversible ADP-ribosylation in mitochondria. EMBO J. 2001;20:2404-12.
21. Nassar OM, Wong KY, Lynch GC, Smith TJ, Pettitt BM. Allosteric discrimination at the NADH/ADP regulatory site of glutamate dehydrogenase. Protein Sci. 2019;28:2080-8.
22. Takeda K, Ishida A, Takahashi K, Ueda T. Synaptic vesicles are capable of synthesizing the VGLUT substrate glutamate from α‐ketoglutarate for vesicular loading. J Neurochem. 2012;121:184-96.
23. Koppula P, Zhang Y, Shi J, Li W, Gan B. The glutamate/cystine antiporter SLC7A11/xCT enhances cancer cell dependency on glucose by exporting glutamate. J Biol Chem. 2017;292:14240-9.
24. Hidalgo C, Arias-Cavieres A. Calcium, reactive oxygen species, and synaptic plasticity. Physiology. 2016;31:201-15.
25. Nissanka N, Moraes CT. Mitochondrial DNA damage and reactive oxygen species in neurodegenerative disease. FEBS Lett. 2018;592:728-42.
26. Wen P, Sun Z, Gou F, et al. Oxidative stress and mitochondrial impairment: key drivers in neurodegenerative disorders. Ageing Res Rev. 2025;104:102667.
27. Kussmaul L, Hirst J. The mechanism of superoxide production by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria. Proc Natl Acad Sci USA. 2006;103:7607-12.
28. Ying W. NAD+/NADH and NADP+/NADPH in cellular functions and cell death: regulation and biological consequences. Antioxid Redox Signal. 2008;10:179-206.
29. Luo L, He Y, Zhao Y, et al. Regulation of mitochondrial NAD pool via NAD+ transporter 2 is essential for matrix NADH homeostasis and ROS production in Arabidopsis. Sci China Life Sci. 2019;62:991-1002.
30. An D, Zeng Q, Zhang P, et al. Alpha-ketoglutarate ameliorates pressure overload-induced chronic cardiac dysfunction in mice. Redox Biol. 2021;46:102088.
31. Yu H, Gan D, Luo Z, et al. α-Ketoglutarate improves cardiac insufficiency through NAD+-SIRT1 signaling-mediated mitophagy and ferroptosis in pressure overload-induced mice. Mol Med. 2024;30:15.
32. He L, Wu J, Tang W, et al. Prevention of oxidative stress by α-ketoglutarate via activation of CAR signaling and modulation of the expression of key antioxidant-associated targets in vivo and in vitro. J Agric Food Chem. 2018;66:11273-83.
33. Zhang Y, Wang H, Zhang Y, et al. α-Ketoglutarate ameliorates sarcopenia in D-galactose-induced aging mice by modulating protein homeostasis and optimizing mitochondrial function. Nutrients. 2025;17:3336.
34. He R, Wei Y, Peng Z, et al. α-Ketoglutarate alleviates osteoarthritis by inhibiting ferroptosis via the ETV4/SLC7A11/GPX4 signaling pathway. Cell Mol Biol Lett. 2024;29:88.
35. Liu S, He L, Yao K. The antioxidative function of alpha-ketoglutarate and its applications. BioMed Res Int. 2018;2018:1-6.
36. Bayliak MM, Shmihel HV, Lylyk MP, et al. Alpha-ketoglutarate attenuates toxic effects of sodium nitroprusside and hydrogen peroxide in Drosophila melanogaster. Environ Toxicol Pharmacol. 2015;40:650-9.
37. Liu Z, Yao X, Jiang W, et al. Advanced oxidation protein products induce microglia-mediated neuroinflammation via MAPKs-NF-κB signaling pathway and pyroptosis after secondary spinal cord injury. J Neuroinflammation. 2020;17:90.
38. Chang Y, He Y, Wang D, et al. ROS-regulated SUR1-TRPM4 drives persistent activation of NLRP3 inflammasome in microglia after whole-brain radiation. Acta Neuropathol Commun. 2025;13:16.
39. Sarkar S, Malovic E, Harishchandra DS, et al. Mitochondrial impairment in microglia amplifies NLRP3 inflammasome proinflammatory signaling in cell culture and animal models of Parkinson’s disease. NPJ Parkinson's Dis. 2017;3:30.
40. Simpson DSA, Oliver PL. ROS generation in microglia: understanding oxidative stress and inflammation in neurodegenerative disease. Antioxidants. 2020;9:743.
41. Gage MC, Thippeswamy T. Inhibitors of src family kinases, inducible nitric oxide synthase, and NADPH oxidase as potential CNS drug targets for neurological diseases. CNS Drugs. 2021;35:1-20.
42. Liu Z, Gan L, Zhang T, Ren Q, Sun C. Melatonin alleviates adipose inflammation through elevating α‐ketoglutarate and diverting adipose‐derived exosomes to macrophages in mice. J Pineal Res. 2017;64:e12455.
43. Lin Z, He H, Chen P, et al. Alpha-ketoglutarate protects against myocardial infarction via FTO-mediated anti-inflammatory macrophage activation. Basic Res Cardiol. 2025;120:889-912.
44. Zhou W, Hu G, He J, et al. SENP1-Sirt3 signaling promotes α-ketoglutarate production during M2 macrophage polarization. Cell Rep. 2022;39:110660.
45. Liu P, Wang H, Li X, et al. α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat Immunol. 2017;18:985-94.
46. Zhu Y, Chen X, Lu Y, et al. Glutamine mitigates murine burn sepsis by supporting macrophage M2 polarization through repressing the SIRT5-mediated desuccinylation of pyruvate dehydrogenase. Burns Trauma. 2022;10:tkac041.
47. Agarwal S, Ghosh R, Verma G, Khadgawat R, Guchhait P. Alpha-ketoglutarate supplementation reduces inflammation and thrombosis in type 2 diabetes by suppressing leukocyte and platelet activation. Clin Exp Immunol. 2023;214:197-208.
48. Jia Y, Yin C, Ke W, et al. Alpha-ketoglutarate alleviates cadmium-induced inflammation by inhibiting the HIF1A-TNFAIP3 pathway in hepatocytes. Sci Total Environ. 2023;878:163069.
49. Zhao J, Kui L, Huang J, et al. Bifidobacterium animalis subsp. Lactis BX-BC08 modulates gut microbiota and secretes alpha-Ketoglutaric acid to alleviate MC903-induced atopic dermatitis. J Transl Med. 2025;23:768.
50. Joshi K, Liu S, Breslin SJP, Zhang J. Mechanisms that regulate the activities of TET proteins. Cell Mol Life Sci. 2022;79:363.
51. Cui X, Zheng Y, Lu Y, Issakidis-Bourguet E, Zhou D. Metabolic control of histone demethylase activity involved in plant response to high temperature. Plant Physiol. 2021;185:1813-28.
52. Ding R, Zhou Y, Zhang Q, et al. Regulation of α-ketoglutarate levels by Myc affects metabolism and demethylation in porcine early embryos. Front Cell Dev Biol. 2024;12:1507102.
53. Carey BW, Finley LWS, Cross JR, Allis CD, Thompson CB. Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature. 2014;518:413-6.
54. Szulwach KE, Li X, Li Y, et al. 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging. Nat Neurosci. 2011;14:1607-16.
55. Traube FR, Özdemir D, Sahin H, et al. Redirected nuclear glutamate dehydrogenase supplies Tet3 with α-ketoglutarate in neurons. Nat Commun. 2021;12:4100.
56. Ren X, Yan J, Zhao Q, et al. The Fe-S cluster assembly protein IscU2 increases α-ketoglutarate catabolism and DNA 5mC to promote tumor growth. Cell Discov. 2023;9:76.
57. Klemmensen MM, Borrowman SH, Pearce C, Pyles B, Chandra B. Mitochondrial dysfunction in neurodegenerative disorders. Neurotherapeutics. 2024;21:e00292.
58. Maurer I. A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients. Neurobiol Aging. 2000;21:455-62.
59. Wang W, Zhao F, Lu Y, et al. Damaged mitochondria coincide with presynaptic vesicle loss and abnormalities in alzheimer’s disease brain. Acta Neuropathol Commun. 2023;11:54.
60. Henrich MT, Oertel WH, Surmeier DJ, Geibl FF. Mitochondrial dysfunction in Parkinson’s disease - a key disease hallmark with therapeutic potential. Mol Neurodegener. 2023;18:83.
61. Schapira AHV, Mann VM, Cooper JM, et al. Anatomic and disease specificity of NADH CoQ1 reductase (Complex I) deficiency in Parkinson's disease. J Neurochem. 2006;55:2142-5.
62. Bouter Y, Glasnek RM, Wenzel JM, Bouter C. 18F-FDG-PET and multimodal biomarker integration: a powerful tool for Alzheimer’s disease diagnosis. Nucl Med Mol Imaging. 2025;59:453-71.
63. Qin L, Crews FT. NADPH oxidase and reactive oxygen species contribute to alcohol-induced microglial activation and neurodegeneration. J Neuroinflammation. 2012;9:5.
64. Ganguly G, Chakrabarti S, Chatterjee U, Saso L. Proteinopathy, oxidative stress and mitochondrial dysfunction: cross talk in Alzheimer's disease and Parkinson's disease. Drug Des Devel Ther. 2017;11:797-810.
65. Thorne NJ, Tumbarello DA. The relationship of alpha-synuclein to mitochondrial dynamics and quality control. Front Mol Neurosci. 2022;15:947191.
66. Chen H, Chan DC. Mitochondrial dynamics-fusion, fission, movement, and mitophagy-in neurodegenerative diseases. Hum Mol Genet. 2009;18:R169-76.
67. Lacombe A, Scorrano L. The interplay between mitochondrial dynamics and autophagy: from a key homeostatic mechanism to a driver of pathology. Semin Cell Dev Biol. 2024;161-2:1-19.
68. Chen W, Zhao H, Li Y. Mitochondrial dynamics in health and disease: mechanisms and potential targets. Sig Transduct Target Ther. 2023;8:333.
69. Navakkode S, Kennedy BK. Alpha‐Ketoglutarate ameliorates synaptic plasticity deficits in APP/PS1 mice model of Alzheimer's disease. Aging Cell. 2025;24:e70235.
70. Yang X, Chen Y, Liu L, et al. Regulation of glycolysis-derived L-lactate production in astrocytes rescues the memory deficits and Aβ burden in early Alzheimer’s disease models. Pharmacol Res. 2024;208:107357.
71. Wang H, Fu J, Xu X, Yang Z, Zhang T. Rapamycin activates mitophagy and alleviates cognitive and synaptic plasticity deficits in a mouse model of Alzheimer’s disease. J Gerontol Series A. 2021;76:1707-13.
72. Su Y, Wang T, Wu N, et al. Alpha-ketoglutarate extends Drosophila lifespan by inhibiting mTOR and activating AMPK. Aging. 2019;11:4183-97.
73. Chin RM, Fu X, Pai MY, et al. The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR. Nature. 2014;510:397-401.
74. Kostiuchenko O, Lushnikova I, Kowalczyk M, Skibo G. mTOR/α-ketoglutarate-mediated signaling pathways in the context of brain neurodegeneration and neuroprotection. BBA Adv. 2022;2:100066.
75. Johnson SC, Kayser E, Bornstein R, et al. Regional metabolic signatures in the Ndufs4(KO) mouse brain implicate defective glutamate/α-ketoglutarate metabolism in mitochondrial disease. Mol Genet Metab. 2020;130:118-32.
76. Neth BJ, Craft S. Insulin resistance and Alzheimer’s disease: bioenergetic linkages. Front Aging Neurosci. 2017;9:345.
77. Pawlosky RJ, Kashiwaya Y, King MT, Veech RL. A dietary ketone ester normalizes abnormal behavior in a mouse model of Alzheimer’s disease. Int J Mol Sci. 2020;21:1044.
78. Nicklas WJ, Vyas I, Heikkila RE. Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. Life Sci. 1985;36:2503-8.
79. Li H, Zhang J, Shen Y, et al. Targeting mitochondrial complex I deficiency in MPP+/MPTP-induced Parkinson’s disease cell culture and mouse models by transducing yeast NDI1 gene. Biol Proced Online. 2024;26:9.
80. Satpute R, Lomash V, Kaushal M, Bhattacharya R. Neuroprotective effects of alpha-ketoglutarate and ethyl pyruvate against motor dysfunction and oxidative changes caused by repeated 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine exposure in mice. Hum Exp Toxicol. 2013;32:747-58.
81. Zhang W, Ding L, Zhang M, et al. Dietary intake of α-ketoglutarate ameliorates α-synuclein pathology in mouse models of Parkinson’s disease. Cell Mol Life Sci. 2023;80:155.
82. Hong S, Beja-Glasser VF, Nfonoyim BM, et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science. 2016;352:712-6.
83. Pisalyaput K, Tenner AJ. Complement component C1q inhibits β‐amyloid‐ and serum amyloid P‐induced neurotoxicity via caspase‐ and calpain‐independent mechanisms. J Neurochem. 2007;104:696-707.
84. Webster SD, Yang AJ, Margol L, Garzon-Rodriguez W, Glabe CG, Tenner AJ. Complement component C1q modulates the phagocytosis of Aβ by microglia. Exp Neurol. 2000;161:127-38.
85. Woollard ML, Pearson RM, Dorf G, Griffith D, James IM. Controlled trial of ornithine alpha ketoglutarate (OAKG) in patients with stroke. Stroke. 1978;9:218-22.
86. Hua W, Zhang X, Tang H, et al. AKG attenuates cerebral ischemia-reperfusion injury through c‐Fos/IL‐10/Stat3 signaling pathway. Oxid Med Cell Longev. 2022;2022:6839385.
87. Tang Y, Han S, Asakawa T, et al. Effects of intracerebral hemorrhage on 5-hydroxymethylcytosine modification in mouse brains. Neuropsychiatr Dis Treat. 2016;2016:617.
88. Ding P, Zhu Q, Sheng B, et al. Alpha‐ketoglutarate alleviates neuronal apoptosis induced by central insulin resistance through inhibiting S6K1 Phosphorylation after subarachnoid hemorrhage. Oxid Med Cell Longev. 2022;2022:9148257.
89. Ari C, Poff AM, Held HE, et al. Metabolic therapy with deanna protocol supplementation delays disease progression and extends survival in amyotrophic lateral sclerosis (ALS) mouse model. PLoS ONE. 2014;9:e103526.
90. Allen SP, Al Sultan A, Kabucho Kibirige E, et al. A Y374X TDP43 truncation leads to an altered metabolic profile in amyotrophic lateral sclerosis fibroblasts driven by pyruvate and TCA cycle intermediate alterations. Front Aging Neurosci. 2023;15:1151848.
91. Ferreira IL, Cunha-Oliveira T, Nascimento MV, et al. Bioenergetic dysfunction in Huntington's disease human cybrids. Exp Neurol. 2011;231:127-34.
92. Niatsetskaya Z, Basso M, Speer RE, et al. HIF prolyl hydroxylase inhibitors prevent neuronal death induced by mitochondrial toxins: therapeutic implications for Huntington's disease and Alzheimer's disease. Antioxid Redox Signal. 2010;12:435-43.
93. Blackman G, Neri G, Al-Doori O, et al. Prevalence of neuroradiological abnormalities in first-episode psychosis: a systematic review and meta-analysis. JAMA Psychiatry. 2023;80:1047.
94. Opel N, Goltermann J, Hermesdorf M, Berger K, Baune BT, Dannlowski U. Cross-disorder analysis of brain structural abnormalities in six major psychiatric disorders: a secondary analysis of mega- and meta-analytical findings from the ENIGMA consortium. Biol Psychiatry. 2020;88:678-86.
95. Doucet GE, Janiri D, Howard R, O’brien M, Andrews-Hanna JR, Frangou S. Transdiagnostic and disease-specific abnormalities in the default-mode network hubs in psychiatric disorders: a meta-analysis of resting-state functional imaging studies. Eur Psychiatry. 2020;63:e57.
96. Ishida T, Nakamura Y, Tanaka SC, et al. Aberrant large-scale network interactions across psychiatric disorders revealed by large-sample multi-site resting-state functional magnetic resonance imaging datasets. Schizophr Bull. 2023;49:933-43.
97. Zhao Z, Li X, Xie Y, et al. Resolving the heterogeneity of dopamine subsystems dysfunction in schizophrenia: a PET meta-analysis. Schizophr. 2025;11:139.
98. Frankle WG, Himes M, Mason NS, Mathis CA, Narendran R. Prefrontal and striatal dopamine release are inversely correlated in schizophrenia. Biol Psychiatry. 2022;92:791-9.
99. Gluck MR, Thomas RG, Davis KL, Haroutunian V. Implications for altered glutamate and GABA metabolism in the dorsolateral prefrontal cortex of aged schizophrenic patients. Am J Psychiatry. 2002;159:1165-73.
100. Campbell IH, Campbell H. The metabolic overdrive hypothesis: hyperglycolysis and glutaminolysis in bipolar mania. Mol Psychiatry. 2024;29:1521-7.
101. Ressler KJ, Nemeroff CB. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress Anxiety. 2000;12:2-19.
102. Nunes PIG, Benjamin SR, Brito RDS, De Aguiar MR, Neves LB, De Bruin VMS. Mitochondria, oxidative stress, and psychiatric disorders: an integrative perspective on brain bioenergetics. Clin Bioenergetics. 2025;1:6.
103. Ni P, Ma Y, Chung S. Mitochondrial dysfunction in psychiatric disorders. Schizophr Res. 2024;273:62-77.
104. Townsend L, Pillinger T, Selvaggi P, Veronese M, Turkheimer F, Howes O. Brain glucose metabolism in schizophrenia: a systematic review and meta-analysis of 18FDG-PET studies in schizophrenia. Psychol Med. 2022;53:4880-97.
105. Rollins BL, Morgan L, Hjelm BE, et al. Mitochondrial complex I deficiency in schizophrenia and bipolar disorder and medication influence. Complex Psychiatry. 2017;3:157-69.
106. Bubber P, Hartounian V, Gibson G, Blass J. Abnormalities in the tricarboxylic acid (TCA) cycle in the brains of schizophrenia patients. Eur Neuropsychopharmacol. 2011;21:254-60.
107. Rangaraju V, Calloway N, Ryan TA. Activity-driven local ATP synthesis is required for synaptic function. Cell. 2014;156:825-35.
108. Davison J, O'gorman A, Brennan L, Cotter DR. A systematic review of metabolite biomarkers of schizophrenia. Schizophr Res. 2018;195:32-50.
109. Xuan J, Pan G, Qiu Y, et al. Metabolomic profiling to identify potential serum biomarkers for schizophrenia and risperidone action. J Proteome Res. 2011;10:5433-43.
110. Cai H, Li H, Yan X, et al. Metabolomic analysis of biochemical changes in the plasma and urine of first-episode neuroleptic-naïve schizophrenia patients after treatment with risperidone. J Proteome Res. 2012;11:4338-50.
111. Paredes RM, Quinones M, Marballi K, et al. Metabolomic profiling of schizophrenia patients at risk for metabolic syndrome. Int J Neuropsychopharm. 2014;17:1139-48.
112. Zhang W, Zhang M, Xu Z, et al. Human forebrain organoid-based multi-omics analyses of PCCB as a schizophrenia associated gene linked to GABAergic pathways. Nat Commun. 2023;14:5176.
113. Yoshimi N, Futamura T, Kakumoto K, et al. Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder. BBA Clin. 2016;5:151-8.
114. Guo Q, Jia J, Sun XL, Yang H, Ren Y. Comparing the metabolic pathways of different clinical phases of bipolar disorder through metabolomics studies. Front Psychiatry. 2024;14:1319870.
115. Kaplan EN, Eren İ, Nazıroğlu M. Mood stabilizers (lamotrigine, lithium, and valproic acid) decrease bipolar disease model (ouabain)‐induced oxidative stress and apoptosis through the inhibition of the TRPM2 channel in neuronal cells. Bipolar Disord. 2025;27:483-500.
116. Eid F, El Ahmad P, Khoury R, et al. α-Ketoglutarate is a circulatory exercise factor that promotes learning and memory recall and has antidepressant properties. Biol Psychiatry Glob Open Sci. 2025;5:100477.
117. Tian J, Peng G, Gao X, et al. Dynamic analysis of the endogenous metabolites in depressed patients treated with TCM formula Xiaoyaosan using urinary 1H NMR-based metabolomics. J Ethnopharmacol. 2014;158:1-10.
118. Demianchuk O, Bayliak M, Vatashchuk M, et al. Alpha-ketoglutarate promotes anxiety, activates autophagy, and suppresses antioxidant enzymes in the cerebral cortex of female mice on cafeteria diet. Brain Res Bull. 2025;222:111255.
119. Ostrom QT, Price M, Neff C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2016-2020. Neuro Oncol. 2023;25:iv1-99.
120. Marin-Valencia I, Yang C, Mashimo T, et al. Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse human glioblastomas in the mouse brain in vivo. Cell Metab. 2012;15:827-37.
121. Deberardinis RJ, Mancuso A, Daikhin E, et al. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA. 2007;104:19345-50.
122. Yang C, Sudderth J, Dang T, Bachoo RG, Mcdonald JG, Deberardinis RJ. Glioblastoma cells require glutamate dehydrogenase to survive impairments of glucose metabolism or akt signaling. Cancer Res. 2009;69:7986-93.
123. Maus A, Peters GJ. Glutamate and α-ketoglutarate: key players in glioma metabolism. Amino Acids. 2016;49:21-32.
124. Ward PS, Patel J, Wise DR, et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate. Cancer Cell. 2010;17:225-34.
125. Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009;462:739-44.
126. Tönjes M, Barbus S, Park YJ, et al. BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1. Nat Med. 2013;19:901-8.
127. Zhang B, Peng H, Zhou M, et al. Targeting BCAT1 combined with α-ketoglutarate triggers metabolic synthetic lethality in glioblastoma. Cancer Res. 2022;82:2388-402.
128. Lewis NA, Klein RH, Kelly C, Yee J, Knoepfler PS. Histone H3.3 K27M chromatin functions implicate a network of neurodevelopmental factors including ASCL1 and NEUROD1 in DIPG. Epigenetics Chromatin. 2022;15:18.
129. Lee K, Yun S, Park J, et al. Dimethyl alpha-ketoglutarate inhibits proliferation in diffuse intrinsic pontine glioma by reprogramming epigenetic and transcriptional networks. Biochem Biophys Res Commun. 2023;677:6-12.
130. Xu W, Yang H, Liu Y, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011;19:17-30.
131. Turcan S, Rohle D, Goenka A, et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature. 2012;483:479-83.
132. Lang F, Kaur K, Fu H, et al. D-2-hydroxyglutarate impairs DNA repair through epigenetic reprogramming. Nat Commun. 2025;16:1431.
133. Wang X, Liu R, Qu X, et al. α-Ketoglutarate-activated NF-κB signaling promotes compensatory glucose uptake and brain tumor development. Mol Cell. 2019;76:148-62.e7.
134. Parker SJ, Encarnación-Rosado J, Hollinshead KER, et al. Spontaneous hydrolysis and spurious metabolic properties of α-ketoglutarate esters. Nat Commun. 2021;12:4905.
135. Baracco EE, Castoldi F, Durand S, et al. α-Ketoglutarate inhibits autophagy. Aging. 2019;11:3418-31.
136. Westi EW, Andersen JV, Aldana BI. Using stable isotope tracing to unravel the metabolic components of neurodegeneration: focus on neuron-glia metabolic interactions. Neurobiol Dis. 2023;182:106145.
