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Cited by 134Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

Glycolytic Metabolism, Brain Resilience, and Alzheimer’s Disease

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Zhang, Xin, Alshakhshir, Nadine, Zhao, Liqin·2021·Frontiers in Neuroscience
DOI 10.3389/fnins.2021.662242PMC PMC8113697
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Abstract

Alzheimer’s disease (AD) is the most common form of age-related dementia. Despite decades of research, the etiology and pathogenesis of AD are not well understood. Brain glucose hypometabolism has long been recognized as a prominent anomaly that occurs in the preclinical stage of AD. Recent studies suggest that glycolytic metabolism, the cytoplasmic pathway of the breakdown of glucose, may play a critical role in the development of AD. Glycolysis is essential for a variety of neural activities in the brain, including energy production, synaptic transmission, and redox homeostasis. Decreased glycolytic flux has been shown to correlate with the severity of amyloid and tau pathology in both preclinical and clinical AD patients. Moreover, increased glucose accumulation found in the brains of AD patients supports the hypothesis that glycolytic deficit may be a contributor to the development of this phenotype. Brain hyperglycemia also provides a plausible explanation for the well-documented link between AD and diabetes. Humans possess three primary variants of the apolipoprotein E (ApoE) gene – ApoE ∗ ϵ2, ApoE ∗ ϵ3, and ApoE ∗ ϵ4 – that confer differential susceptibility to AD. Recent findings indicate that neuronal glycolysis is significantly affected by human ApoE isoforms and glycolytic robustness may serve as a major mechanism that renders an ApoE2-bearing brain more resistant against the neurodegenerative risks for AD. In addition to AD, glycolytic dysfunction has been observed in other neurodegenerative diseases, including Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis, strengthening the concept of glycolytic dysfunction as a common pathway leading to neurodegeneration. Taken together, these advances highlight a promising translational opportunity that involves targeting glycolysis to bolster brain metabolic resilience and by such to alter the course of brain aging or disease development to prevent or reduce the risks for not only AD but also other neurodegenerative diseases.

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  • Elevated glycolysis has been viewed as a potential compensatory response to mitochondrial dysfunction after exposure to AD plasma, serving as an early indicator of cellular energy deficiency.

    “Elevated glycolysis has been viewed as a potential compensatory response to mitochondrial dysfunction after exposure to AD plasma, serving as an early indicator of cellular energy deficiency [26,27].”

    From APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons (2024) · cites this paper as [27]

  • Brain metabolic changes can be influenced by APOE genetic variation.

    “These changes in brain metabolism can be influenced by APOE genetic variation [12][13][14] .”

    From APOE4-drives brain bioenergetic shifts independent of Alzheimer’s disease pathology (2026) · cites this paper as [12]

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  1. Achariyar T. M. Li B. Peng W. Verghese P. B. Shi Y. McConnell E. (2016). Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation. Mol. Neurodegener. 11: 74. 10.1186/s13024-016-0138-8 27931262 PMC5146863 · DOI
  2. Agostini M. Romeo F. Inoue S. Niklison-Chirou M. V. Elia A. J. Dinsdale D. (2016). Metabolic reprogramming during neuronal differentiation. Cell Death Differ. 23 1502– 1514. 10.1038/cdd.2016.36 27058317 PMC5072427 · DOI
  3. Alexandre V. Yves L. Rémy G. Jean-Noël V. (2018). Aerobic glycolysis in amyotrophic lateral sclerosis and Huntington’s disease. Rev. Neurosci. 29 547– 555. 10.1515/revneuro-2017-0075 29303786 · DOI
  4. Amtul Z. (2016). Why therapies for Alzheimer’s disease do not work: do we have consensus over the path to follow? Ageing Res. Rev. 25 70– 84. 10.1016/j.arr.2015.09.003 26375861 · DOI
  5. An Y. Varma V. R. Varma S. Casanova R. Dammer E. Pletnikova O. (2018). Evidence for brain glucose dysregulation in Alzheimer’s disease. Alzheimers Dement. 14 318– 329. 10.1016/j.jalz.2017.09.011 29055815 PMC5866736 · DOI
  6. Aoki K. Uchihara T. Sanjo N. Nakamura A. Ikeda K. Tsuchiya K. (2003). Increased expression of neuronal apolipoprotein E in human brain with cerebral infarction. Stroke 34 875– 880. 10.1161/01.Str.0000064320.73388.C6 12649507 · DOI
  7. Arenaza-Urquijo E. M. Vemuri P. (2018). Resistance vs resilience to Alzheimer disease: clarifying terminology for preclinical studies. Neurology 90 695– 703. 10.1212/WNL.0000000000005303 29592885 PMC5894932 · DOI
  8. Arvanitakis Z. Wilson R. S. Bienias J. L. Evans D. A. Bennett D. A. (2004). Diabetes mellitus and risk of Alzheimer Disease and decline in cognitive function. Arch. Neurol. 61 661– 666. 10.1001/archneur.61.5.661 15148141 · DOI · Paper page
  9. Attwell D. Iadecola C. (2002). The neural basis of functional brain imaging signals. Trends Neurosci. 25 621– 625. 10.1016/s0166-2236(02)02264-6 12446129 · DOI · Paper page
  10. Barros L. F. (2013). Metabolic signaling by lactate in the brain. Trends Neurosci. 36 396– 404. 10.1016/j.tins.2013.04.002 23639382 · DOI
  11. Bartzokis G. Lu P. H. Geschwind D. H. Edwards N. Mintz J. Cummings J. L. (2006). Apolipoprotein E genotype and age-related myelin breakdown in healthy individuals: implications for cognitive decline and dementia. Arch. Gen. Psychiatry 63 63– 72. 10.1001/archpsyc.63.1.63 16389198 · DOI
  12. Bauernfeind A. L. Barks S. K. Duka T. Grossman L. I. Hof P. R. Sherwood C. C. (2014). Aerobic glycolysis in the primate brain: reconsidering the implications for growth and maintenance. Brain Struct. Funct. 219 1149– 1167. 10.1007/s00429-013-0662-z 24185460 · DOI · Paper page
  13. Bergau N. Maul S. Rujescu D. Simm A. Navarrete Santos A. (2019). Reduction of glycolysis intermediate concentrations in the cerebrospinal fluid of Alzheimer’s Disease patients. Front. Neurosci. 13: 871. 10.3389/fnins.2019.00871 31496932 PMC6713159 · DOI
  14. Bergersen L. H. Magistretti P. J. Pellerin L. (2005). Selective postsynaptic co-localization of MCT2 with AMPA receptor GluR2/3 subunits at excitatory synapses exhibiting AMPA receptor trafficking. Cereb. Cortex 15 361– 370. 10.1093/cercor/bhh138 15749979 · DOI
  15. Bermejo P. Martín-Aragón S. Benedí J. Susín C. Felici E. Gil P. (2008). Peripheral levels of glutathione and protein oxidation as markers in the development of Alzheimer’s disease from mild cognitive impairment. Free Radic. Res. 42 162– 170. 10.1080/10715760701861373 18297609 · DOI
  16. Berthet C. Castillo X. Magistretti P. J. Hirt L. (2012). New evidence of neuroprotection by lactate after transient focal cerebral ischaemia: extended benefit after intracerebroventricular injection and efficacy of intravenous administration. Cerebrovasc. Dis. 34 329– 335. 10.1159/000343657 23154656 · DOI
  17. Bigl M. Bruckner M. K. Arendt T. Bigl V. Eschrich K. (1999). Activities of key glycolytic enzymes in the brains of patients with Alzheimer’s disease. J. Neural Transm. 106 499– 511. 10.1007/s007020050174 10443553 · DOI
  18. Bojarski L. Herms J. Kuznicki J. (2008). Calcium dysregulation in Alzheimer’s disease. Neurochem. Int. 52 621– 633. 10.1016/j.neuint.2007.10.002 18035450 · DOI
  19. Boschert U. Merlo-Pich E. Higgins G. Roses A. D. Catsicas S. (1999). Apolipoprotein E expression by neurons surviving excitotoxic stress. Neurobiol. Dis. 6 508– 514. 10.1006/nbdi.1999.0251 10600406 · DOI
  20. Bowen D. M. White P. Spillane J. A. Goodhardt M. J. Curzon G. Iwangoff P. (1979). Accelerated ageing or selective neuronal loss as an important cause of dementia? Lancet 1 11– 14. 10.1016/s0140-6736(79)90454-9 83462 · DOI
  21. Brand K. A. Hermfisse U. (1997). Aerobic glycolysis by proliferating cells: a protective strategy against reactive oxygen species. Faseb J. 11 388– 395. 10.1096/fasebj.11.5.9141507 9141507 · DOI · Paper page
  22. Cai R. Zhang Y. Simmering J. E. Schultz J. L. Li Y. Fernandez-Carasa I. (2019). Enhancing glycolysis attenuates Parkinson’s disease progression in models and clinical databases. J. Clin. Invest. 129 4539– 4549. 10.1172/jci129987 31524631 PMC6763248 · DOI · Paper page
  23. Canzoniero L. M. Snider B. J. (2005). Calcium in Alzheimer’s disease pathogenesis: too much, too little or in the wrong place? J. Alzheimers Dis. 8 147– 154. 10.3233/jad-2005-8207 discussion 209-115 16308483 · DOI
  24. Chaiyawat P. Chokchaichamnankit D. Lirdprapamongkol K. Srisomsap C. Svasti J. Champattanachai V. (2015). Alteration of O-GlcNAcylation affects serine phosphorylation and regulates gene expression and activity of pyruvate kinase M2 in colorectal cancer cells. Oncol. Rep. 34 1933– 1942. 10.3892/or.2015.4178 26252736 · DOI
  25. Chan C. Y. Dominguez D. Parra K. J. (2016). Regulation of Vacuolar H+-ATPase (V-ATPase) reassembly by glycolysis flow in 6-Phosphofructo-1-kinase (PFK-1)-deficient yeast cells. J. Biol. Chem. 291 15820– 15829. 10.1074/jbc.M116.717488 27226568 PMC4957063 · DOI · Paper page
  26. Chen X. Levy J. M. Hou A. Winters C. Azzam R. Sousa A. A. (2015). PSD-95 family MAGUKs are essential for anchoring AMPA and NMDA receptor complexes at the postsynaptic density. Proc. Natl. Acad. Sci. U.S.A. 112 E6983– E6992. 10.1073/pnas.1517045112 26604311 PMC4687590 · DOI · Paper page
  27. Chen Z. Zhong C. (2013). Decoding Alzheimer’s disease from perturbed cerebral glucose metabolism: implications for diagnostic and therapeutic strategies. Prog. Neurobiol. 108 21– 43. 10.1016/j.pneurobio.2013.06.004 23850509 · DOI
  28. Chun Y. S. Kwon O. H. Chung S. (2017). O-GlcNAcylation of amyloid-β precursor protein at threonine 576 residue regulates trafficking and processing. Biochem. Biophys. Res. Commun. 490 486– 491. 10.1016/j.bbrc.2017.06.067 28624365 · DOI
  29. Costantini L. C. Barr L. J. Vogel J. L. Henderson S. T. (2008). Hypometabolism as a therapeutic target in Alzheimer’s disease. BMC Neurosci. 9(Suppl. 2): S16. 10.1186/1471-2202-9-S2-S16 19090989 PMC2604900 · DOI · Paper page
  30. de la Monte S. M. Tong M. (2014). Brain metabolic dysfunction at the core of Alzheimer’s disease. Biochem. Pharmacol. 88 548– 559. 10.1016/j.bcp.2013.12.012 24380887 PMC4550323 · DOI
  31. de la Monte S. M. Wands J. R. (2008). Alzheimer’s disease is type 3 diabetes-evidence reviewed. J. Diabetes Sci. Technol. 2 1101– 1113. 10.1177/193229680800200619 19885299 PMC2769828 · DOI · Paper page
  32. de Leon M. J. Convit A. Wolf O. T. Tarshish C. Y. DeSanti S. Rusinek H. (2001). Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET). Proc. Natl. Acad. Sci. U.S.A. 98 10966– 10971. 10.1073/pnas.191044198 11526211 PMC58582 · DOI · Paper page
  33. Demarin V. Podobnik S. S. Storga-Tomic D. Kay G. (2004). Treatment of Alzheimer’s disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study. Drugs Exp. Clin. Res. 30 27– 33. 15134388
  34. Drzezga A. Lautenschlager N. Siebner H. Riemenschneider M. Willoch F. Minoshima S. (2003). Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer’s disease: a PET follow-up study. Eur. J. Nucl. Med. Mol. Imaging 30 1104– 1113. 10.1007/s00259-003-1194-1 12764551 · DOI
  35. Dumitrescu L. Mahoney E. Mukherjee S. Lee M. Bush W. Engelman C. (2020). Genetic variants and functional pathways associated with resilience to Alzheimer’s disease. Brain 143 2561– 2575. 10.1093/brain/awaa209 32844198 PMC7447518 · DOI
  36. Esteves A. R. Domingues A. F. Ferreira I. L. Januario C. Swerdlow R. H. Oliveira C. R. (2008). Mitochondrial function in Parkinson’s disease cybrids containing an nt2 neuron-like nuclear background. Mitochondrion 8 219– 228. 10.1016/j.mito.2008.03.004 18495557 · DOI
  37. Filosto M. Tomelleri G. Tonin P. Scarpelli M. Vattemi G. Rizzuto N. (2007). Neuropathology of mitochondrial diseases. Biosci. Rep. 27 23– 30. 10.1007/s10540-007-9034-3 17541738 · DOI
  38. Fisher G. H. D’Aniello A. Vetere A. Padula L. Cusano G. P. Man E. H. (1991). Free D-aspartate and D-alanine in normal and Alzheimer brain. Brain Res. Bull. 26 983– 985. 10.1016/0361-9230(91)90266-m 1933416 · DOI
  39. Fleck M. W. Henze D. A. Barrionuevo G. Palmer A. M. (1993). Aspartate and glutamate mediate excitatory synaptic transmission in area CA1 of the hippocampus. J. Neurosci. 13 3944– 3955. 10.1523/jneurosci.13-09-03944.1993 7690067 PMC6576443 · DOI
  40. Fukuyama H. Ogawa M. Yamauchi H. Yamaguchi S. Kimura J. Yonekura Y. (1994). Altered cerebral energy metabolism in Alzheimer’s disease: a PET study. J. Nucl. Med. 35 1– 6. 8271029
  41. Gallogly M. M. Mieyal J. J. (2007). Mechanisms of reversible protein glutathionylation in redox signaling and oxidative stress. Curr. Opin. Pharmacol. 7 381– 391. 10.1016/j.coph.2007.06.003 17662654 · DOI
  42. Ganapathy-Kanniappan S. Geschwind J.-F. H. (2013). Tumor glycolysis as a target for cancer therapy: progress and prospects. Mol. Cancer 12: 152. 10.1186/1476-4598-12-152 24298908 PMC4223729 · DOI
  43. Gao X. Lee K. Reid M. A. Sanderson S. M. Qiu C. Li S. (2018). Serine availability influences mitochondrial dynamics and function through lipid metabolism. Cell Rep. 22 3507– 3520. 10.1016/j.celrep.2018.03.017 29590619 PMC6054483 · DOI
  44. Ghesquiere B. Wong B. W. Kuchnio A. Carmeliet P. (2014). Metabolism of stromal and immune cells in health and disease. Nature 511 167– 176. 10.1038/nature13312 25008522 · DOI
  45. Goncalves J. Bartol T. M. Camus C. Levet F. Menegolla A. P. Sejnowski T. J. (2020). Nanoscale co-organization and coactivation of AMPAR, NMDAR, and mGluR at excitatory synapses. Proc. Natl. Acad. Sci. U.S.A. 117: 14503. 10.1073/pnas.1922563117 32513712 PMC7321977 · DOI · Paper page
  46. Gong L. Shu H. He C. Ye Q. Bai F. Xie C. (2017). Convergent and divergent effects of apolipoprotein E ε4 and ε2 alleles on amygdala functional networks in nondemented older adults. Neurobiol. Aging 54 31– 39. 10.1016/j.neurobiolaging.2017.02.013 28319835 · DOI
  47. Gordon G. R. Choi H. B. Rungta R. L. Ellis-Davies G. C. MacVicar B. A. (2008). Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature 456 745– 749. 10.1038/nature07525 18971930 PMC4097022 · DOI
  48. Goyal M. S. Gordon B. A. Couture L. E. Flores S. Xiong C. Morris J. C. (2020). Spatiotemporal relationship between subthreshold amyloid accumulation and aerobic glycolysis in the human brain. Neurobiol. Aging 96 165– 175. 10.1016/j.neurobiolaging.2020.08.019 33011615 PMC7894981 · DOI
  49. Goyal M. S. Vlassenko A. G. Blazey T. M. Su Y. Couture L. E. Durbin T. J. (2017). Loss of brain aerobic glycolysis in normal human aging. Cell Metab. 26 353.e3– 360.e3. 10.1016/j.cmet.2017.07.010 28768174 PMC5573225 · DOI · Paper page
  50. Grothe M. J. Villeneuve S. Dyrba M. Bartrés-Faz D. Wirth M. (2017). Multimodal characterization of older APOE2 carriers reveals selective reduction of amyloid load. Neurology 88 569– 576. 10.1212/wnl.0000000000003585 28062720 PMC5304459 · DOI
  51. Groves J. A. Lee A. Yildirir G. Zachara N. E. (2013). Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis. Cell Stress Chaperones 18 535– 558. 10.1007/s12192-013-0426-y 23620203 PMC3745259 · DOI
  52. Gruetter R. Ugurbil K. Seaquist E. R. (1998). Steady-state cerebral glucose concentrations and transport in the human brain. J. Neurochem. 70 397– 408. 10.1046/j.1471-4159.1998.70010397.x 9422387 · DOI
  53. Gu J. H. Shi J. Dai C. L. Ge J. B. Zhao Y. Chen Y. (2017). O-GlcNAcylation reduces ischemia-reperfusion-induced brain injury. Sci. Rep. 7: 10686. 10.1038/s41598-017-10635-0 28878265 PMC5587588 · DOI
  54. Guercio G. D. Panizzutti R. (2018). Potential and challenges for the clinical use of d-Serine as a cognitive enhancer. Front. Psychiatry 9: 14. 10.3389/fpsyt.2018.00014 29459833 PMC5807334 · DOI
  55. Guo C. Zhang S. Li J.-Y. Ding C. Yang Z.-H. Chai R. (2016). Chronic hyperglycemia induced via the heterozygous knockout of Pdx1 worsens neuropathological lesion in an Alzheimer mouse model. Sci. Rep. 6 29396– 29396. 10.1038/srep29396 27406855 PMC4942607 · DOI
  56. Hamilton J. A. Hillard C. J. Spector A. A. Watkins P. A. (2007). Brain uptake and utilization of fatty acids, lipids and lipoproteins: application to neurological disorders. J. Mol. Neurosci. 33 2– 11. 10.1007/s12031-007-0060-1 17901539 · DOI
  57. Harris R. A. Tindale L. Lone A. Singh O. Macauley S. L. Stanley M. (2016). Aerobic glycolysis in the frontal cortex correlates with memory performance in wild-type mice but not the APP/PS1 mouse model of cerebral amyloidosis. J. Neurosci. 36 1871– 1878. 10.1523/jneurosci.3131-15.2016 26865611 PMC4748073 · DOI
  58. Harrison J. R. Owen M. J. (2016). Alzheimer’s disease: the amyloid hypothesis on trial. Br. J. Psychiatry 208 1– 3. 10.1192/bjp.bp.115.167569 26729836 · DOI
  59. Hashimoto K. Fukushima T. Shimizu E. Okada S. Komatsu N. Okamura N. (2004). Possible role of D-serine in the pathophysiology of Alzheimer’s disease. Prog. Neuropsychopharmacol. Biol. Psychiatry 28 385– 388. 14751437
  60. Hou Y. Lautrup S. Cordonnier S. Wang Y. Croteau D. L. Zavala E. (2018). NAD(+) supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. Proc. Natl. Acad. Sci. U.S.A. 115 E1876– E1885. 10.1073/pnas.1718819115 29432159 PMC5828618 · DOI · Paper page
  61. Howarth C. (2014). The contribution of astrocytes to the regulation of cerebral blood flow. Front. Neurosci. 8: 103. 10.3389/fnins.2014.00103 24847203 PMC4023041 · DOI
  62. Hoyer S. Nitsch R. Oesterreich K. (1991). Predominant abnormality in cerebral glucose utilization in late-onset dementia of the Alzheimer type: a cross-sectional comparison against advanced late-onset and incipient early-onset cases. J. Neural Transm. Park. Dis. Dement. Sect. 3 1– 14. 10.1007/bf02251132 1905936 · DOI
  63. Hoyer S. Oesterreich K. Wagner O. (1988). Glucose metabolism as the site of the primary abnormality in early-onset dementia of Alzheimer type? J. Neurol. 235 143– 148. 10.1007/bf00314304 3367161 · DOI
  64. Huang Q. Sun M. Li M. Zhang D. Han F. Wu J. C. (2018). Combination of NAD(+) and NADPH offers greater neuroprotection in ischemic stroke models by relieving metabolic stress. Mol. Neurobiol. 55 6063– 6075. 10.1007/s12035-017-0809-7 29164394 · DOI
  65. Huttenlocher P. R. Dabholkar A. S. (1997). Regional differences in synaptogenesis in human cerebral cortex. J. Comp. Neurol. 387 167– 178. 10.1002/(SICI)1096-9861(19971020)387:2<167::AID-CNE1<3.0.CO;2-Z 9336221 · DOI
  66. Hwang H. Rhim H. (2018). Functional significance of O-GlcNAc modification in regulating neuronal properties. Pharmacol. Res. 129 295– 307. 10.1016/j.phrs.2017.12.006 29223644 · DOI
  67. Hyder F. Patel A. B. Gjedde A. Rothman D. L. Behar K. L. Shulman R. G. (2006). Neuronal-glial glucose oxidation and glutamatergic-GABAergic function. J. Cereb. Blood Flow. Metab. 26 865– 877. 10.1038/sj.jcbfm.9600263 16407855 · DOI · Paper page
  68. Ishitani R. Chuang D. M. (1996). Glyceraldehyde-3-phosphate dehydrogenase antisense oligodeoxynucleotides protect against cytosine arabinonucleoside-induced apoptosis in cultured cerebellar neurons. Proc. Natl. Acad. Sci. U.S.A. 93 9937– 9941. 10.1073/pnas.93.18.9937 8790435 PMC38533 · DOI
  69. Itakura M. Nakajima H. Kubo T. Semi Y. Kume S. Higashida S. (2015). Glyceraldehyde-3-phosphate dehydrogenase aggregates accelerate amyloid-β amyloidogenesis in Alzheimer Disease. J. Biol. Chem. 290 26072– 26087. 10.1074/jbc.M115.669291 26359500 PMC4646260 · DOI
  70. Jacob R. J. Fan X. Evans M. L. Dziura J. Sherwin R. S. (2002). Brain glucose levels are elevated in chronically hyperglycemic diabetic rats: no evidence for protective adaptation by the blood brain barrier. Metab. Clin. Exp. 51 1522– 1524. 10.1053/meta.2002.36347 12489061 · DOI
  71. Jacobsen K. T. Iverfeldt K. (2011). O-GlcNAcylation increases non-amyloidogenic processing of the amyloid-β precursor protein (APP). Biochem. Biophys. Res. Commun. 404 882– 886. 10.1016/j.bbrc.2010.12.080 21182826 · DOI
  72. Jang S. Nelson J. C. Bend E. G. Rodriguez-Laureano L. Tueros F. G. Cartagenova L. (2016). Glycolytic enzymes localize to synapses under energy stress to support synaptic function. Neuron 90 278– 291. 10.1016/j.neuron.2016.03.011 27068791 PMC4840048 · DOI · Paper page
  73. Janson J. Laedtke T. Parisi J. E. O’Brien P. Petersen R. C. Butler P. C. (2004). Increased Risk of Type 2 Diabetes in Alzheimer Disease. Diabetes 53 474– 481. 10.2337/diabetes.53.2.474 14747300 · DOI · Paper page
  74. Jayasena T. Poljak A. Braidy N. Smythe G. Raftery M. Hill M. (2015). Upregulation of glycolytic enzymes, mitochondrial dysfunction and increased cytotoxicity in glial cells treated with Alzheimer’s disease plasma. PLoS One 10: e0116092. 10.1371/journal.pone.0116092 25785936 PMC4364672 · DOI · Paper page
  75. Kam K. Nicoll R. (2007). Excitatory synaptic transmission persists independently of the glutamate–glutamine cycle. J. Neurosci. 27 9192– 9200. 10.1523/JNEUROSCI.1198-07.2007 17715355 PMC6672195 · DOI
  76. Kao Y.-C. Ho P.-C. Tu Y.-K. Jou I. M. Tsai K.-J. (2020). Lipids and Alzheimer’s Disease. Int. J. Mol. Sci. 21: 1505. 10.3390/ijms21041505 32098382 PMC7073164 · DOI · Paper page
  77. Katsouri L. Ashraf A. de Belleroche J. Sastre M. (2011). D-Serine synthesis and metabolism in the Alzheimer’s brain. Alzheimer’s Dement. 7: S702. 10.1016/j.jalz.2011.05.2031 · DOI
  78. Keeney J. T. Ibrahimi S. Zhao L. (2015). Human ApoE isoforms differentially modulate glucose and amyloid metabolic pathways in female brain: evidence of the mechanism of neuroprotection by ApoE2 and implications for Alzheimer’s Disease prevention and early intervention. J. Alzheimers Dis. 48 411– 424. 10.3233/jad-150348 26402005 PMC5485924 · DOI · Paper page
  79. Khatri N. Man H.-Y. (2013). Synaptic activity and bioenergy homeostasis: implications in brain trauma and neurodegenerative diseases. Front. Neurol. 4: 199. 10.3389/fneur.2013.00199 24376435 PMC3858785 · DOI
  80. Kish S. J. Lopes-Cendes I. Guttman M. Furukawa Y. Pandolfo M. Rouleau G. A. (1998). Brain glyceraldehyde-3-phosphate dehydrogenase activity in human trinucleotide repeat disorders. Arch. Neurol. 55 1299– 1304. 10.1001/archneur.55.10.1299 9779656 · DOI
  81. Knoferle J. Yoon S. Y. Walker D. Leung L. Gillespie A. K. Tong L. M. (2014). Apolipoprotein E4 produced in GABAergic interneurons causes learning and memory deficits in mice. J. Neurosci. 34 14069– 14078. 10.1523/JNEUROSCI.2281-14.2014 25319703 PMC4198545 · DOI · Paper page
  82. Kohio H. P. Adamson A. L. (2013). Glycolytic control of vacuolar-type ATPase activity: a mechanism to regulate influenza viral infection. Virology 444 301– 309. 10.1016/j.virol.2013.06.026 23876457 · DOI
  83. Konttinen H. Cabral-da-Silva M. E. C. Ohtonen S. Wojciechowski S. Shakirzyanova A. Caligola S. (2019). PSEN1ΔE9, APPswe, and APOE4 Confer disparate phenotypes in human iPSC-Derived Microglia. Stem Cell Rep. 13 669– 683. 10.1016/j.stemcr.2019.08.004 31522977 PMC6829767 · DOI · Paper page
  84. Krstic D. Knuesel I. (2013). Deciphering the mechanism underlying late-onset Alzheimer disease. Nat. Rev. Neurol. 9 25– 34. 10.1038/nrneurol.2012.236 23183882 · DOI · Paper page
  85. Lauretti E. Li J. G. Di Meco A. Praticò D. (2017). Glucose deficit triggers tau pathology and synaptic dysfunction in a tauopathy mouse model. Trans. Psychiatry 7: e1020. 10.1038/tp.2016.296 28140402 PMC5299397 · DOI
  86. Lazarev V. F. Guzhova I. V. Margulis B. A. (2020). Glyceraldehyde-3-phosphate dehydrogenase is a multifaceted therapeutic target. Pharmaceutics 12: 416. 10.3390/pharmaceutics12050416 32370188 PMC7285110 · DOI
  87. Le Bras A. (2019). Glycolysis in Parkinson’s disease. Lab Anim. 48 330– 330. 10.1038/s41684-019-0430-7 · DOI
  88. Le Douce J. Maugard M. Veran J. Matos M. Jégo P. Vigneron P. A. (2020). Impairment of glycolysis-derived l-serine production in astrocytes contributes to cognitive deficits in Alzheimer’s Disease. Cell Metab. 31 503.e8– 517.e8. 10.1016/j.cmet.2020.02.004 32130882 · DOI
  89. Li M. Zhou Z. P. Sun M. Cao L. Chen J. Qin Y. Y. (2016). Reduced nicotinamide adenine dinucleotide phosphate, a pentose phosphate pathway product. might be a novel drug candidate for ischemic stroke. Stroke 47 187– 195. 10.1161/strokeaha.115.009687 26564104 · DOI
  90. Li Z. Okamoto K.-I. Hayashi Y. Sheng M. (2004). The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119 873– 887. 10.1016/j.cell.2004.11.003 15607982 · DOI · Paper page
  91. Liu F. Shi J. Tanimukai H. Gu J. Gu J. Grundke-Iqbal I. (2009). Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer’s disease. Brain 132(Pt 7) 1820– 1832. 10.1093/brain/awp099 19451179 PMC2702834 · DOI · Paper page
  92. Liu Z. Patil I. Y. Jiang T. Sancheti H. Walsh J. P. Stiles B. L. (2015). High-fat diet induces hepatic insulin resistance and impairment of synaptic plasticity. PLoS One 10: e0128274. 10.1371/journal.pone.0128274 26023930 PMC4449222 · DOI
  93. Lu M. Holliday L. S. Zhang L. Dunn W. A. Jr. Gluck S. L. (2001). Interaction between aldolase and vacuolar H+-ATPase: evidence for direct coupling of glycolysis to the ATP-hydrolyzing proton pump. J. Biol. Chem. 276 30407– 30413. 10.1074/jbc.M008768200 11399750 · DOI
  94. Lu M. Sautin Y. Y. Holliday L. S. Gluck S. L. (2004). The glycolytic enzyme aldolase mediates assembly, expression, and activity of vacuolar H+-ATPase. J. Biol. Chem. 279 8732– 8739. 10.1074/jbc.M303871200 14672945 · DOI
  95. Lying-Tunell U. Lindblad B. S. Malmlund H. O. Persson B. (1981). Cerebral blood flow and metabolic rate of oxygen, glucose, lactate, pyruvate, ketone bodies and amino acids. Acta Neurol. Scand. 63 337– 350. 10.1111/j.1600-0404.1981.tb00788.x 7324866 · DOI
  96. MacVicar B. A. Newman E. A. (2015). Astrocyte regulation of blood flow in the brain. Cold Spring Harbor Perspect. Biol. 7: a020388. 10.1101/cshperspect.a020388 25818565 PMC4448617 · DOI
  97. Maddocks O. D. Labuschagne C. F. Vousden K. H. (2014). Localization of NADPH production: a wheel within a wheel. Mol. Cell 55 158– 160. 10.1016/j.molcel.2014.07.001 25038411 · DOI
  98. Madeira C. Lourenco M. V. Vargas-Lopes C. Suemoto C. K. Brandão C. O. Reis T. (2015). d-serine levels in Alzheimer’s disease: implications for novel biomarker development. Trans. Psychiatry 5: e561. 10.1038/tp.2015.52 25942042 PMC4471283 · DOI
  99. Magistretti P. J. (2014). Synaptic plasticity and the warburg effect. Cell Metab. 19 4– 5. 10.1016/j.cmet.2013.12.012 24411936 · DOI
  100. Magistretti P. J. Allaman I. (2018). Lactate in the brain: from metabolic end-product to signalling molecule. Nat. Rev. Neurosci. 19 235– 249. 10.1038/nrn.2018.19 29515192 · DOI · Paper page
  101. Malone J. I. Hanna S. Saporta S. Mervis R. F. Park C. R. Chong L. (2008). Hyperglycemia not hypoglycemia alters neuronal dendrites and impairs spatial memory. Pediatr. Diabetes 9 531– 539. 10.1111/j.1399-5448.2008.00431.x 19067891 · DOI
  102. Malonek D. Grinvald A. (1996). Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping. Science 272 551– 554. 10.1126/science.272.5261.551 8614805 · DOI
  103. Manzo E. Lorenzini I. Barrameda D. O’Conner A. G. Barrows J. M. Starr A. (2019). Glycolysis upregulation is neuroprotective as a compensatory mechanism in ALS. eLife 8: e45114. 10.7554/eLife.45114 31180318 PMC6557627 · DOI
  104. Marcus D. L. de Leon M. J. Goldman J. Logan J. Christman D. R. Wolf A. P. (1989). Altered glucose metabolism in microvessels from patients with Alzheimer’s disease. Ann. Neurol. 26 91– 94. 10.1002/ana.410260114 2774504 · DOI
  105. Marder E. Goaillard J. M. (2006). Variability, compensation and homeostasis in neuron and network function. Nat. Rev. Neurosci. 7 563– 574. 10.1038/nrn1949 16791145 · DOI · Paper page
  106. Margineanu M. B. Mahmood H. Fiumelli H. Magistretti P. J. (2018). L-lactate regulates the expression of synaptic plasticity and neuroprotection genes in cortical neurons: a transcriptome analysis. Front. Mol. Neurosci. 11: 375. 10.3389/fnmol.2018.00375 30364173 PMC6191511 · DOI
  107. Marshall S. Bacote V. Traxinger R. R. (1991). Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance. J. Biol. Chem. 266 4706– 4712. 10.1016/s0021-9258(19)67706-9 2002019 · DOI
  108. Mason S. (2017). Lactate Shuttles in neuroenergetics-homeostasis, allostasis and beyond. Front. Neurosci. 11: 43. 10.3389/fnins.2017.00043 28210209 PMC5288365 · DOI
  109. Massa M. L. Gagliardino J. J. Francini F. (2011). Liver glucokinase: an overview on the regulatory mechanisms of its activity. IUBMB Life 63 1– 6. 10.1002/iub.411 21280170 · DOI
  110. Matsumaru S. Oguni H. Ogura H. Shimojima K. Nagata S. Kanno H. (2017). A novel PGK1 mutation associated with neurological dysfunction and the absence of episodes of hemolytic anemia or myoglobinuria. Intractable Rare Dis. Res. 6 132– 136. 10.5582/irdr.2017.01020 28580215 PMC5451746 · DOI
  111. Maughan R. (2009). Carbohydrate metabolism. Surg. Oxford Int. Ed. 27 6– 10. 10.1016/j.mpsur.2008.12.002 · DOI · Paper page
  112. Mazzola J. L. Sirover M. A. (2001). Reduction of glyceraldehyde-3-phosphate dehydrogenase activity in Alzheimer’s disease and in Huntington’s disease fibroblasts. J. Neurochem. 76 442– 449. 10.1046/j.1471-4159.2001.00033.x 11208907 · DOI
  113. McLarty J. L. Marsh S. A. Chatham J. C. (2013). Post-translational protein modification by O-linked N-acetyl-glucosamine: its role in mediating the adverse effects of diabetes on the heart. Life Sci. 92 621– 627. 10.1016/j.lfs.2012.08.006 22985933 PMC3528804 · DOI
  114. Mejías R. Villadiego J. Pintado C. O. Vime P. J. Gao L. Toledo-Aral J. J. (2006). Neuroprotection by transgenic expression of glucose-6-phosphate dehydrogenase in dopaminergic nigrostriatal neurons of mice. J. Neurosci. 26 4500– 4508. 10.1523/JNEUROSCI.0122-06.2006 16641229 PMC6674068 · DOI
  115. Milewski S. Gabriel I. Olchowy J. (2006). Enzymes of UDP-GlcNAc biosynthesis in yeast. Yeast 23 1– 14. 10.1002/yea.1337 16408321 · DOI
  116. Moriyama Y. Futai M. (1990). H(+)-ATPase, a primary pump for accumulation of neurotransmitters, is a major constituent of brain synaptic vesicles. Biochem. Biophys. Res. Commun. 173 443– 448. 10.1016/s0006-291x(05)81078-2 1979489 · DOI
  117. Moriyama Y. Maeda M. Futai M. (1992). The role of V-ATPase in neuronal and endocrine systems. J. Exp. Biol. 172 171– 178. 1362770
  118. Morris C. M. Benjamin R. Leake A. McArthur F. K. Candy J. M. Ince P. G. (1995). Effect of apolipoprotein E genotype on Alzheimer’s disease neuropathology in a cohort of elderly Norwegians. Neurosci. Lett. 201 45– 47. 10.1016/0304-3940(94)12126-b 8830309 · DOI · Paper page
  119. Mortilla M. Sorbi S. (1990). [Hexokinase in Alzheimer’s disease]. Medicina 10 168– 169. 2273956
  120. Mosconi L. (2005). Brain glucose metabolism in the early and specific diagnosis of Alzheimer’s disease. FDG-PET studies in MCI and AD. Eur. J. Nucl. Med. Mol. Imaging 32 486– 510. 10.1007/s00259-005-1762-7 15747152 · DOI
  121. Mosconi L. De Santi S. Brys M. Tsui W. H. Pirraglia E. Glodzik-Sobanska L. (2008a). Hypometabolism and altered cerebrospinal fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints. Biol. Psychiatry 63 609– 618. 10.1016/j.biopsych.2007.05.030 17720148 PMC2386268 · DOI · Paper page
  122. Mosconi L. De Santi S. Li J. Tsui W. H. Li Y. Boppana M. (2008b). Hippocampal hypometabolism predicts cognitive decline from normal aging. Neurobiol. Aging 29 676– 692. 10.1016/j.neurobiolaging.2006.12.008 17222480 PMC2430185 · DOI · Paper page
  123. Mosconi L. Pupi A. De Leon M. J. (2008c). Brain glucose hypometabolism and oxidative stress in preclinical Alzheimer’s disease. Ann. N. Y. Acad. Sci. 1147 180– 195. 10.1196/annals.1427.007 19076441 PMC2661241 · DOI
  124. Mosconi L. Sorbi S. de Leon M. J. Li Y. Nacmias B. Myoung P. S. (2006). Hypometabolism exceeds atrophy in presymptomatic early-onset familial Alzheimer’s disease. J. Nucl. Med. 47 1778– 1786. 17079810
  125. Nagy Z. Esiri M. M. Jobst K. A. Johnston C. Litchfield S. Sim E. (1995). Influence of the apolipoprotein E genotype on amyloid deposition and neurofibrillary tangle formation in Alzheimer’s disease. Neuroscience 69 757– 761. 10.1016/0306-4522(95)00331-c 8596645 · DOI · Paper page
  126. Nakajima H. Amano W. Kubo T. Fukuhara A. Ihara H. Azuma Y. T. (2009). Glyceraldehyde-3-phosphate dehydrogenase aggregate formation participates in oxidative stress-induced cell death. J. Biol. Chem. 284 34331– 34341. 10.1074/jbc.M109.027698 19837666 PMC2797201 · DOI
  127. Nakamura S. (2004). Glucose activates H(+)-ATPase in kidney epithelial cells. Am. J. Physiol. Cell Physiol. 287 C97– C105. 10.1152/ajpcell.00469.2003 15189820 · DOI
  128. Newington J. T. Pitts A. Chien A. Arseneault R. Schubert D. Cumming R. C. (2011). Amyloid beta resistance in nerve cell lines is mediated by the Warburg effect. PLoS One 6: e19191. 10.1371/journal.pone.0019191 21541279 PMC3082554 · DOI
  129. Newington J. T. Rappon T. Albers S. Wong D. Y. Rylett R. J. Cumming R. C. (2012). Overexpression of pyruvate dehydrogenase kinase 1 and lactate dehydrogenase A in nerve cells confers resistance to amyloid beta and other toxins by decreasing mitochondrial respiration and reactive oxygen species production. J. Biol. Chem. 287 37245– 37258. 10.1074/jbc.M112.366195 22948140 PMC3481323 · DOI
  130. Newman S. F. Sultana R. Perluigi M. Coccia R. Cai J. Pierce W. M. (2007). An increase in S-glutathionylated proteins in the Alzheimer’s disease inferior parietal lobule, a proteomics approach. J. Neurosci. Res. 85 1506– 1514. 10.1002/jnr.21275 17387692 · DOI
  131. Niemeyer H. Ureta T. Clark-Turri L. (1975). Adaptive character of liver glucokinase. Mol. Cell Biochem. 6 109– 126. 10.1007/bf01732005 164620 · DOI
  132. Nusser Z. Mulvihill E. Streit P. Somogyi P. (1994). Subsynaptic segregation of metabotropic and ionotropic glutamate receptors as revealed by immunogold localization. Neuroscience 61 421– 427. 10.1016/0306-4522(94)90421-9 7969918 · DOI
  133. Ohara T. Doi Y. Ninomiya T. Hirakawa Y. Hata J. Iwaki T. (2011). Glucose tolerance status and risk of dementia in the community: the hisayama study. Neurology 7 1126– 1134. 10.1212/WNL.0b013e31822f0435 21931106 · DOI
  134. Orosz F. Oláh J. Ovádi J. (2008). Triosephosphate isomerase deficiency: facts and doubts. IUBMB Life 58 703– 715. 10.1080/15216540601115960 17424909 · DOI
  135. Owen O. E. (2006). Ketone bodies as a fuel for the brain during starvation. Biochem.Mol. Biol.Educ. 33 246– 251. 10.1002/bmb.2005.49403304246 · DOI
  136. Paradies G. Paradies V. De Benedictis V. Ruggiero F. M. Petrosillo G. (2014). Functional role of cardiolipin in mitochondrial bioenergetics. Biochim. Biophys. Acta 1837 408– 417. 10.1016/j.bbabio.2013.10.006 24183692 · DOI
  137. Patra K. C. Hay N. (2014). The pentose phosphate pathway and cancer. Trends Biochem. Sci. 39 347– 354. 10.1016/j.tibs.2014.06.005 25037503 PMC4329227 · DOI
  138. Patterson R. L. van Rossum D. B. Kaplin A. I. Barrow R. K. Snyder S. H. (2005). Inositol 1,4,5-trisphosphate receptor/GAPDH complex augments Ca2+ release via locally derived NADH. Proc. Natl. Acad. Sci. U.S.A. 102 1357– 1359. 10.1073/pnas.0409657102 15677321 PMC547892 · DOI
  139. Pearce E. L. Poffenberger M. C. Chang C. H. Jones R. G. (2013). Fueling immunity: insights into metabolism and lymphocyte function. Science 342: 1242454. 10.1126/science.1242454 24115444 PMC4486656 · DOI · Paper page
  140. Pellerin L. Bouzier-Sore A. K. Aubert A. Serres S. Merle M. Costalat R. (2007). Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55 1251– 1262. 10.1002/glia.20528 17659524 · DOI · Paper page
  141. Pellerin L. Magistretti P. J. (1996). Excitatory amino acids stimulate aerobic glycolysis in astrocytes via an activation of the Na+/K+ ATPase. Dev. Neurosci. 18 336– 342. 10.1159/000111426 8940604 · DOI
  142. Perry G. Cash A. D. Smith M. A. (2002). Alzheimer Disease and oxidative stress. J. Biomed. Biotechnol. 2 120– 123. 10.1155/S1110724302203010 12488575 PMC161361 · DOI · Paper page
  143. Pfeiffer T. Schuster S. Bonhoeffer S. (2001). Cooperation and competition in the evolution of ATP-producing pathways. Science 292 504– 507. 10.1126/science.1058079 11283355 · DOI
  144. Pilkis S. J. El-Maghrabi M. R. McGrane M. Pilkis J. Claus T. H. (1982). Regulation by glucagon of hepatic pyruvate kinase, 6-phosphofructo 1-kinase, and fructose-1,6-bisphosphatase. Fed. Proc. 41 2623– 2628. 6286362
  145. Powers W. J. Videen T. O. Markham J. McGee-Minnich L. Antenor-Dorsey J. V. Hershey T. (2007). Selective defect of in vivo glycolysis in early Huntington’s disease striatum. Proc. Natl. Acad. Sci. U.S.A. 104 2945– 2949. 10.1073/pnas.0609833104 17299049 PMC1797149 · DOI
  146. Prentki M. Madiraju S. R. (2008). Glycerolipid metabolism and signaling in health and disease. Endocr. Rev. 29 647– 676. 10.1210/er.2008-0007 18606873 · DOI
  147. Ralser M. Wamelink M. M. Kowald A. Gerisch B. Heeren G. Struys E. A. (2007). Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress. J. Biol. 6: 10. 10.1186/jbiol61 18154684 PMC2373902 · DOI
  148. Rao X. Duan X. Mao W. Li X. Li Z. Li Q. (2015). O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth. Nat. Commun. 6: 8468. 10.1038/ncomms9468 26399441 PMC4598839 · DOI
  149. Reiman E. M. Caselli R. J. Chen K. Alexander G. E. Bandy D. Frost J. (2001). Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: a foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer’s disease. Proc. Natl. Acad. Sci. U.S.A. 98 3334– 3339. 10.1073/pnas.061509598 11248079 PMC30654 · DOI · Paper page
  150. Reiman E. M. Caselli R. J. Yun L. S. Chen K. Bandy D. Minoshima S. (1996). Preclinical evidence of Alzheimer’s disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N. Engl. J. Med. 334 752– 758. 10.1056/nejm199603213341202 8592548 · DOI · Paper page
  151. Reiman E. M. Chen K. Alexander G. E. Caselli R. J. Bandy D. Osborne D. (2004). Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer’s dementia. Proc. Natl. Acad. Sci. U.S.A. 101 284– 289. 10.1073/pnas.2635903100 14688411 PMC314177 · DOI · Paper page
  152. Rocher A. B. Chapon F. Blaizot X. Baron J. C. Chavoix C. (2003). Resting-state brain glucose utilization as measured by PET is directly related to regional synaptophysin levels: a study in baboons. Neuroimage 20 1894– 1898. 10.1016/j.neuroimage.2003.07.002 14642499 · DOI · Paper page
  153. Rodriguez-Rodriguez P. Almeida A. Bolaños J. P. (2013). Brain energy metabolism in glutamate-receptor activation and excitotoxicity: role for APC/C-Cdh1 in the balance glycolysis/pentose phosphate pathway. Neurochem. Int. 62 750– 756. 10.1016/j.neuint.2013.02.005 23416042 · DOI
  154. Ros J. Pecinska N. Alessandri B. Landolt H. Fillenz M. (2001). Lactate reduces glutamate-induced neurotoxicity in rat cortex. J. Neurosci. Res. 66 790– 794. 10.1002/jnr.10043 11746403 · DOI
  155. Sakaue S. Kasai T. Mizuta I. Suematsu M. Osone S. Azuma Y. (2017). Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: do PGK-1 mutations contribute to vulnerability to parkinsonism? NPJ Parkinson’s Dis. 3: 13. 10.1038/s41531-017-0014-4 28649613 PMC5459803 · DOI
  156. Sameni S. Syed A. Marsh J. L. Digman M. A. (2016). The phasor-FLIM fingerprints reveal shifts from OXPHOS to enhanced glycolysis in Huntington Disease. Sci. Rep. 6: 34755. 10.1038/srep34755 27713486 PMC5054433 · DOI
  157. Schlame M. Brody S. Hostetler K. Y. (1993). Mitochondrial cardiolipin in diverse eukaryotes. Comparison of biosynthetic reactions and molecular acyl species. Eur. J. Biochem. 212 727– 735. 10.1111/j.1432-1033.1993.tb17711.x 8385010 · DOI
  158. Schlame M. Horvàth L. Vìgh L. (1990). Relationship between lipid saturation and lipid-protein interaction in liver mitochondria modified by catalytic hydrogenation with reference to cardiolipin molecular species. Biochem. J. 265 79– 85. 10.1042/bj2650079 2154183 PMC1136616 · DOI
  159. Schleicher E. D. Weigert C. (2000). Role of the hexosamine biosynthetic pathway in diabetic nephropathy. Kidney Int. Suppl. 77 S13– S18. 10997685
  160. Schmitz J. P. Groenendaal W. Wessels B. Wiseman R. W. Hilbers P. A. Nicolay K. (2013). Combined in vivo and in silico investigations of activation of glycolysis in contracting skeletal muscle. Am. J. Physiol. Cell Physiol. 304 C180– C193. 10.1152/ajpcell.00101.2012 23114964 PMC3546809 · DOI
  161. Seaquist E. R. Tkac I. Damberg G. Thomas W. Gruetter R. (2005). Brain glucose concentrations in poorly controlled diabetes mellitus as measured by high-field magnetic resonance spectroscopy. Metabolism 54 1008– 1013. 10.1016/j.metabol.2005.02.018 16092049 · DOI
  162. Segarra-Mondejar M. Casellas-Díaz S. Ramiro-Pareta M. Müller-Sánchez C. Martorell-Riera A. Hermelo I. (2018). Synaptic activity-induced glycolysis facilitates membrane lipid provision and neurite outgrowth. Embo J. 37: e97368. 10.15252/embj.201797368 29615453 PMC5920244 · DOI
  163. Shannon B. J. Vaishnavi S. N. Vlassenko A. G. Shimony J. S. Rutlin J. Raichle M. E. (2016). Brain aerobic glycolysis and motor adaptation learning. Proc. Natl. Acad. Sci. U.S.A. 113: E3782. PMC4932971 27217563
  164. Shimizu J. Kasai T. Yoshida H. Huynh A. M. Nakao-Azuma Y. Shinomoto M. (2020). Novel Drosophila model for parkinsonism by targeting phosphoglycerate kinase. Neurochem. Int. 139: 104816. 10.1016/j.neuint.2020.104816 32758590 · DOI
  165. Silbereis J. C. Pochareddy S. Zhu Y. Li M. Sestan N. (2016). The cellular and molecular landscapes of the developing human central nervous system. Neuron 89 248– 268. 10.1016/j.neuron.2015.12.008 26796689 PMC4959909 · DOI · Paper page
  166. Silver I. A. Erecinska M. (1994). Extracellular glucose concentration in mammalian brain: continuous monitoring of changes during increased neuronal activity and upon limitation in oxygen supply in normo-, hypo-, and hyperglycemic animals. J. Neurosci. 14 5068– 5076. 10.1523/JNEUROSCI.14-08-05068.1994 8046468 PMC6577171 · DOI
  167. Sims N. R. Blass J. P. Murphy C. Bowen D. M. Neary D. (1987). Phosphofructokinase activity in the brain in Alzheimer’s disease. Ann. Neurol. 21 509– 510. 10.1002/ana.410210517 2954507 · DOI
  168. Sims N. R. Bowen D. M. Smith C. C. Flack R. H. Davison A. N. Snowden J. S. (1980). Glucose metabolism and acetylcholine synthesis in relation to neuronal activity in Alzheimer’s disease. Lancet 1 333– 336. 10.1016/s0140-6736(80)90884-3 6101790 · DOI
  169. Skorobogatko Y. V. Deuso J. Adolf-Bryfogle J. Nowak M. G. Gong Y. Lippa C. F. (2011). Human Alzheimer’s disease synaptic O-GlcNAc site mapping and iTRAQ expression proteomics with ion trap mass spectrometry. Amino Acids 40 765– 779. 10.1007/s00726-010-0645-9 20563614 · DOI
  170. Skovronsky D. M. Lee V. M. Trojanowski J. Q. (2006). Neurodegenerative diseases: new concepts of pathogenesis and their therapeutic implications. Annu. Rev. Pathol. 1 151– 170. 10.1146/annurev.pathol.1.110304.100113 18039111 · DOI
  171. Söderberg M. Edlund C. Kristensson K. Dallner G. (1991). Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease. Lipids 26 421– 425. 10.1007/bf02536067 1881238 · DOI · Paper page
  172. Sorbi S. Mortilla M. Piacentini S. Tonini S. Amaducci L. (1990). Altered hexokinase activity in skin cultured fibroblasts and leukocytes from Alzheimer’s disease patients. Neurosci. Lett. 117 165– 168. 10.1016/0304-3940(90)90138-y 2149746 · DOI
  173. Sotiriou E. Greene P. Krishna S. Hirano M. Dimauro S. (2010). Myopathy and Parkinsonism in phosphoglycerate kinase deficiency. Muscle Nerve 41 707– 710. 10.1002/mus.21612 20151463 PMC8285082 · DOI
  174. Soucek T. Cumming R. Dargusch R. Maher P. Schubert D. (2003). The regulation of glucose metabolism by HIF-1 mediates a neuroprotective response to amyloid beta peptide. Neuron 39 43– 56. 10.1016/S0896-6273(03)00367-2 12848931 · DOI · Paper page
  175. Stanton R. C. (2012). Glucose-6-phosphate dehydrogenase. NADPH, and cell survival. IUBMB Life 64 362– 369. 10.1002/iub.1017 22431005 PMC3325335 · DOI
  176. Steen E. Terry B. M. Rivera J. E. Cannon J. L. Neely T. R. Tavares R. (2005). Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease – is this type 3 diabetes? J. Alzheimer’s Dis. 7 63– 80. 10.3233/JAD-2005-7107 15750215 · DOI · Paper page
  177. Steiner P. (2019). Brain fuel utilization in the developing brain. Ann. Nutr. Metab. 75 8– 18. 10.1159/000508054 32564020 · DOI
  178. Su Y. Zhou A. Al-Lamki R. S. Karet F. E. (2003). The a-subunit of the V-type H+-ATPase interacts with phosphofructokinase-1 in humans. J. Biol. Chem. 278 20013– 20018. 10.1074/jbc.M210077200 12649290 · DOI
  179. Suzuki M. Sasabe J. Miyoshi Y. Kuwasako K. Muto Y. Hamase K. (2015). Glycolytic flux controls D-serine synthesis through glyceraldehyde-3-phosphate dehydrogenase in astrocytes. Proc. Natl. Acad. Sci. U.S.A. 112 E2217– E2224. 10.1073/pnas.1416117112 25870284 PMC4418896 · DOI
  180. Svennerholm L. (1968). Distribution and fatty acid composition of phosphoglycerides in normal human brain. J. Lipid Res. 9 570– 579. 10.1016/s0022-2275(20)42702-6 4302302 · DOI
  181. Takata T. Okada Y. (1995). Effects of deprivation of oxygen or glucose on the neural activity in the guinea pig hippocampal slice–intracellular recording study of pyramidal neurons. Brain Res. 683 109– 116. 10.1016/0006-8993(95)00318-k 7552335 · DOI
  182. Tarze A. Deniaud A. Le Bras M. Maillier E. Molle D. Larochette N. (2007). GAPDH, a novel regulator of the pro-apoptotic mitochondrial membrane permeabilization. Oncogene 26 2606– 2620. 10.1038/sj.onc.1210074 17072346 · DOI
  183. Tedeschi P. M. Markert E. K. Gounder M. Lin H. Dvorzhinski D. Dolfi S. C. (2013). Contribution of serine, folate and glycine metabolism to the ATP, NADPH and purine requirements of cancer cells. Cell Death Dis. 4: e877. 10.1038/cddis.2013.393 24157871 PMC3920946 · DOI
  184. The HD iPSC Consortium (2019). Bioenergetic deficits in Huntington’s disease iPSC-derived neural cells and rescue with glycolytic metabolites. Hum. Mol. Genet. 29 1757– 1771. 10.1093/hmg/ddy430 30768179 PMC7372552 · DOI
  185. Theurey P. Connolly N. M. C. Fortunati I. Basso E. Lauwen S. Ferrante C. (2019). Systems biology identifies preserved integrity but impaired metabolism of mitochondria due to a glycolytic defect in Alzheimer’s disease neurons. Aging Cell 18: e12924. 10.1111/acel.12924 30793475 PMC6516149 · DOI
  186. Torlinska K. Grochowalska A. Kupsz J. Skoracka J. Kojo S. (2006). In vivo and in vitro effects of hyperglycemia on Na+ -K+, Ca+2, Mg+2-dependent ATPases activity in brain synaptosomes of aging rats. J. Physiol. Pharmacol. 57(Suppl. 7), 145– 158. 10.1016/0741-8329(85)90032-1 17228102 · DOI
  187. Trinidad J. C. Barkan D. T. Gulledge B. F. Thalhammer A. Sali A. Schoepfer R. (2012). Global identification and characterization of both O-GlcNAcylation and phosphorylation at the murine synapse. Mol. Cell Proteomics 11 215– 229. 10.1074/mcp.O112.018366 22645316 PMC3412957 · DOI
  188. Uchihara T. Duyckaerts C. He Y. Kobayashi K. Seilhean D. Amouyel P. (1995). ApoE immunoreactivity and microglial cells in Alzheimer’s disease brain. Neurosci. Lett. 195 5– 8. 10.1016/0304-3940(95)11763-m 7478253 · DOI · Paper page
  189. Vaishnavi S. N. Vlassenko A. G. Rundle M. M. Snyder A. Z. Mintun M. A. Raichle M. E. (2010). Regional aerobic glycolysis in the human brain. Proc. Natl. Acad. Sci. U.S.A. 107 17757– 17762. 20837536 PMC2955101
  190. Velasco A. Tan Z. (2014). “ Fatty acids and the aging brain,” in Omega-3 Fatty Acids in Brain and Neurological Health, ed. Watson R. R. (Amsterdam: Elsevier Science).
  191. Vlassenko A. G. Gordon B. A. Goyal M. S. Su Y. Blazey T. M. Durbin T. J. (2018). Aerobic glycolysis and tau deposition in preclinical Alzheimer’s disease. Neurobiol. Aging 67 95– 98. 10.1016/j.neurobiolaging.2018.03.014 29655050 PMC5955846 · DOI · Paper page
  192. Vlassenko A. G. Raichle M. E. (2015). Brain aerobic glycolysis functions and Alzheimer’s disease. Clin. Transl. Imaging 3 27– 37. 10.1007/s40336-014-0094-7 26855936 PMC4743905 · DOI
  193. Voloboueva L. A. Emery J. F. Sun X. Giffard R. G. (2013). Inflammatory response of microglial BV-2 cells includes a glycolytic shift and is modulated by mitochondrial glucose-regulated protein 75/mortalin. FEBS Lett. 587 756– 762. 10.1016/j.febslet.2013.01.067 23395614 PMC3603371 · DOI
  194. Vosseller K. Trinidad J. C. Chalkley R. J. Specht C. G. Thalhammer A. Lynn A. J. (2006). O-linked N-acetylglucosamine proteomics of postsynaptic density preparations using lectin weak affinity chromatography and mass spectrometry. Mol. Cell Proteomics 5 923– 934. 10.1074/mcp.T500040-MCP200 16452088 · DOI
  195. Wang K. C. Woung L. C. Tsai M. T. Liu C. C. Su Y. H. Li C. Y. (2012). Risk of Alzheimer’s disease in relation to diabetes: a population-based cohort study. Neuroepidemiology 38 237– 244. 10.1159/000337428 22572745 · DOI
  196. Wang Y. Liu J. Jin X. Zhang D. Li D. Hao F. (2017). O-GlcNAcylation destabilizes the active tetrameric PKM2 to promote the Warburg effect. Proc. Natl. Acad. Sci. U.S.A. 114 13732– 13737. 10.1073/pnas.1704145115 29229835 PMC5748163 · DOI
  197. Wang Y. Wu L. Li J. Fang D. Zhong C. Chen J. X. (2015). Synergistic exacerbation of mitochondrial and synaptic dysfunction and resultant learning and memory deficit in a mouse model of diabetic Alzheimer’s disease. J. Alzheimers Dis. 43 451– 463. 10.3233/jad-140972 25096625 PMC4466096 · DOI
  198. Warburg O. (1956). On the origin of cancer cells. Science 123 309– 314. 13298683
  199. Wells L. Hart G. W. (2003). O-GlcNAc turns twenty: functional implications for post-translational modification of nuclear and cytosolic proteins with a sugar. FEBS Lett. 546 154– 158. 10.1016/s0014-5793(03)00641-0 12829252 · DOI
  200. Wells L. Vosseller K. Hart G. W. (2001). Glycosylation of nucleocytoplasmic proteins: signal transduction and O-GlcNAc. Science 291 2376– 2378. 10.1126/science.1058714 11269319 · DOI

200 of 216 shown

Cited by

Sorted by citations

Authors
Zhang, X., Alshakhshir, N., & Zhao, L.
Affiliations
University of Kansas (US)
Corresponding author
Zhao, Liqin
ORCID
Zhang, Xin
Venue
Frontiers in Neuroscience
Publisher
Frontiers Media SA
Published
2021-04-28
Volume
15
Pages
662242-662242
ISSN
1662-453X (ISSN-L)
DOI
10.3389/fnins.2021.662242
PMC
PMC8113697
OpenAlex
W3157462717
Cited by
134
References
27
Citations by year
2026: 29 · 2025: 32 · 2024: 24 · 2023: 22 · 2022: 17 · 2021: 10
FWCI
2.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • KU ScholarWorks (The University of Kansas) (submittedVersion, cc-by)
Funders
  • National Institutes of Health
  • National Institute on Aging (R21AG059177, R01AG061038, R21AG055964, R01AG071682)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Alzheimer's disease, glycolysis, brain glucose metabolism, brain glucose hypometabolism, apolipoprotein E isoforms, APOE ε4, amyloid pathology, tau pathology, neurodegeneration, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, diabetes mellitus, brain aging

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