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Cited by 11Alzheimer's disease research and treatmentsMitochondrial Function and PathologyDementia and Cognitive Impairment Research

Systemic Metabolism and Mitochondria in the Mechanism of Alzheimer’s Disease: Finding Potential Therapeutic Targets

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Song, Meiying, Fan, Xiang·2023·International Journal of Molecular Sciences
DOI 10.3390/ijms24098398PMC PMC10179273
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Abstract

Elderly people over the age of 65 are those most likely to experience Alzheimer’s disease (AD), and aging and AD are associated with apparent metabolic alterations. Currently, there is no curative medication against AD and only several drugs have been approved by the FDA, but these drugs can only improve the symptoms of AD. Many preclinical and clinical trials have explored the impact of adjusting the whole-body and intracellular metabolism on the pathogenesis of AD. The most recent evidence suggests that mitochondria initiate an integrated stress response to environmental stress, which is beneficial for healthy aging and neuroprotection. There is also an increasing awareness of the differential risk and potential targeting strategies related to the metabolic level and microbiome. As the main participants in intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been regarded as potential therapeutic targets for AD. This review summarizes and highlights these advances.

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  • Mitochondrial dysfunction in AD is characterized by reduced ATP production, impaired OXPHOS, decreased respiratory complex activity, loss of membrane potential, disrupted Ca2+ buffering, and defective transport along axons and dendrites.

    “At the cellular level, mitochondrial dysfunction in AD is characterized by reduced ATP production, impaired oxidative phosphorylation (OXPHOS), decreased activity of respiratory complexes, loss of membrane potential, disrupted Ca2+ buffering, and defective transport along axons and dendrites [57].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [57]

    Section 3.1 reports reduced ATP levels, decreased respiratory capacity, and Ca2+ dyshomeostasis in AD; the Introduction reports abnormal electron-transport-chain activity, and section 3.3 describes Aβ-associated loss of mitochondrial membrane potential. The copy does not specifically establish decreased activity of individual respiratory complexes or defective mitochondrial transport along axons and dendrites: section 3.3 links altered mitochondrial distribution there to OPA1 deficiency in neurons. (LLM, conf=0.84)

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  1. [2]Alzheimer’s Association 2022 Alzheimer’s disease facts and figures Alzheimer’s Dement. J. Alzheimer’s Assoc. 2022 18 700 789 10.1002/alz.12638 35289055 · DOI
  2. [3]Hoyer S. Glucose metabolism and insulin receptor signal transduction in Alzheimer disease Eur. J. Pharmacol. 2004 490 115 125 10.1016/j.ejphar.2004.02.049 15094078 · DOI
  3. [4]Hölscher C. Diabetes as a risk factor for Alzheimer’s disease: Insulin signalling impairment in the brain as an alternative model of Alzheimer’s disease Biochem. Soc. Trans. 2011 39 891 897 10.1042/BST0390891 21787319 · DOI
  4. [5]Cheng G. Huang C. Deng H. Wang H. Diabetes as a risk factor for dementia and mild cognitive impairment: A meta-analysis of longitudinal studies Intern. Med. J. 2012 42 484 491 10.1111/j.1445-5994.2012.02758.x 22372522 · DOI · Paper page
  5. [7]Koekkoek P.S. Kappelle L.J. van den Berg E. Rutten G.E. Biessels G.J. Cognitive function in patients with diabetes mellitus: Guidance for daily care Lancet Neurol. 2015 14 329 340 10.1016/S1474-4422(14)70249-2 25728442 · DOI
  6. [9]Kandimalla R. Thirumala V. Reddy P.H. Is Alzheimer’s disease a Type 3 Diabetes? A critical appraisal Biochim. Biophys. Acta Mol. Basis Dis. 2017 1863 1078 1089 10.1016/j.bbadis.2016.08.018 27567931 PMC5344773 · DOI · Paper page
  7. [10]Szablewski L. Glucose Transporters in Brain: In Health and in Alzheimer’s Disease J. Alzheimer’s Dis. 2017 55 1307 1320 10.3233/JAD-160841 27858715 · DOI · Paper page
  8. [11]Pugazhenthi S. Qin L. Reddy P.H. Common neurodegenerative pathways in obesity, diabetes, and Alzheimer’s disease Biochim. Biophys. Acta Mol. Basis Dis. 2017 1863 1037 1045 10.1016/j.bbadis.2016.04.017 27156888 PMC5344771 · DOI · Paper page
  9. [12]Kubis-Kubiak A.M. Rorbach-Dolata A. Piwowar A. Crucial players in Alzheimer’s disease and diabetes mellitus: Friends or foes? Mech. Ageing Dev. 2019 181 7 21 10.1016/j.mad.2019.03.008 31085195 · DOI
  10. [13]Macklin L. Griffith C.M. Cai Y. Rose G.M. Yan X.X. Patrylo P.R. Glucose tolerance and insulin sensitivity are impaired in APP/PS1 transgenic mice prior to amyloid plaque pathogenesis and cognitive decline Exp. Gerontol. 2017 88 9 18 10.1016/j.exger.2016.12.019 28025127 · DOI
  11. [14]Biessels G.J. Kamal A. Ramakers G.M. Urban I.J. Spruijt B.M. Erkelens D.W. Gispen W.H. Place learning and hippocampal synaptic plasticity in streptozotocin-induced diabetic rats Diabetes 1996 45 1259 1266 10.2337/diab.45.9.1259 8772732 · DOI
  12. [15]Huang H.J. Liang K.C. Chen C.P. Chen C.M. Hsieh-Li H.M. Intrahippocampal administration of A beta(1-40) impairs spatial learning and memory in hyperglycemic mice Neurobiol. Learn. Mem. 2007 87 483 494 10.1016/j.nlm.2006.11.006 17241793 · DOI
  13. [16]Sena L.A. Chandel N.S. Physiological roles of mitochondrial reactive oxygen species Mol. Cell 2012 48 158 167 10.1016/j.molcel.2012.09.025 23102266 PMC3484374 · DOI · Paper page
  14. [17]Angelova P.R. Abramov A.Y. Functional role of mitochondrial reactive oxygen species in physiology Free Radic. Biol. Med. 2016 100 81 85 10.1016/j.freeradbiomed.2016.06.005 27296839 · DOI
  15. [18]Abramov A.Y. Scorziello A. Duchen M.R. Three distinct mechanisms generate oxygen free radicals in neurons and contribute to cell death during anoxia and reoxygenation J. Neurosci. Off. J. Soc. Neurosci. 2007 27 1129 1138 10.1523/JNEUROSCI.4468-06.2007 PMC6673180 17267568 · DOI
  16. [19]Gandhi S. Abramov A.Y. Mechanism of oxidative stress in neurodegeneration Oxidative Med. Cell. Longev. 2012 2012 428010 10.1155/2012/428010 PMC3362933 22685618 · DOI
  17. [20]Gandhi S. Vaarmann A. Yao Z. Duchen M.R. Wood N.W. Abramov A.Y. Dopamine induced neurodegeneration in a PINK1 model of Parkinson’s disease PLoS ONE 2012 7 e37564 10.1371/journal.pone.0037564 22662171 PMC3360782 · DOI
  18. [21]Li P. Nijhawan D. Budihardjo I. Srinivasula S.M. Ahmad M. Alnemri E.S. Wang X. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade Cell 1997 91 479 489 10.1016/S0092-8674(00)80434-1 9390557 · DOI · Paper page
  19. [22]Du C. Fang M. Li Y. Li L. Wang X. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition Cell 2000 102 33 42 10.1016/S0092-8674(00)00008-8 10929711 · DOI · Paper page
  20. [23]Bock F.J. Tait S.W.G. Mitochondria as multifaceted regulators of cell death Nat. Rev. Mol. Cell Biol. 2020 21 85 100 10.1038/s41580-019-0173-8 31636403 · DOI
  21. [24]Gibson G.E. Luchsinger J.A. Cirio R. Chen H. Franchino-Elder J. Hirsch J.A. Bettendorff L. Chen Z. Flowers S.A. Gerber L.M. Benfotiamine and Cognitive Decline in Alzheimer’s Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial J. Alzheimer’s Dis. 2020 78 989 1010 10.3233/JAD-200896 33074237 PMC7880246 · DOI
  22. [25]Hoffman J.M. Welsh-Bohmer K.A. Hanson M. Crain B. Hulette C. Earl N. Coleman R.E. FDG PET imaging in patients with pathologically verified dementia J. Nucl. Med. Off. Publ. Soc. Nucl. Med. 2000 41 1920 1928 11079505
  23. [26]Vincent C. Hall P.A. Executive Function in Adults with Type 2 Diabetes: A Meta-Analytic Review Psychosom. Med. 2015 77 631 642 10.1097/PSY.0000000000000103 25469685 · DOI
  24. [27]Hall K.D. Heymsfield S.B. Kemnitz J.W. Klein S. Schoeller D.A. Speakman J.R. Energy balance and its components: Implications for body weight regulation Am. J. Clin. Nutr. 2012 95 989 994 10.3945/ajcn.112.036350 22434603 PMC3302369 · DOI · Paper page
  25. [29]Jimenez A. Pegueroles J. Carmona-Iragui M. Vilaplana E. Montal V. Alcolea D. Videla L. Illán-Gala I. Pané A. Casajoana A. Weight loss in the healthy elderly might be a non-cognitive sign of preclinical Alzheimer’s disease Oncotarget 2017 8 104706 104716 10.18632/oncotarget.22218 29285207 PMC5739594 · DOI
  26. [30]2Alford S. Patel D. Perakakis N. Mantzoros C.S. Obesity as a risk factor for Alzheimer’s disease: Weighing the evidence Obes. Rev. Off. J. Int. Assoc. Study Obes. 2018 19 269 280 10.1111/obr.12629 29024348 · DOI
  27. [31]Vidoni E.D. Townley R.A. Honea R.A. Burns J.M. Alzheimer disease biomarkers are associated with body mass index Neurology 2011 77 1913 1920 10.1212/WNL.0b013e318238eec1 22105948 PMC3233188 · DOI
  28. [32]Ewers M. Schmitz S. Hansson O. Walsh C. Fitzpatrick A. Bennett D. Minthon L. Trojanowski J.Q. Shaw L.M. Faluyi Y.O. Body mass index is associated with biological CSF markers of core brain pathology of Alzheimer’s disease Neurobiol. Aging 2012 33 1599 1608 10.1016/j.neurobiolaging.2011.05.005 21684041 PMC3208117 · DOI
  29. [33]James D. Kang S. Park S. Injection of β-amyloid into the hippocampus induces metabolic disturbances and involuntary weight loss which may be early indicators of Alzheimer’s disease Aging Clin. Exp. Res. 2014 26 93 98 10.1007/s40520-013-0181-z 24399640 · DOI
  30. [34]Liguori C. Chiaravalloti A. Sancesario G. Stefani A. Sancesario G.M. Mercuri N.B. Schillaci O. Pierantozzi M. Cerebrospinal fluid lactate levels and brain [18F]FDG PET hypometabolism within the default mode network in Alzheimer’s disease Eur. J. Nucl. Med. Mol. Imaging 2016 43 2040 2049 10.1007/s00259-016-3417-2 27221635 · DOI
  31. [35]Redjems-Bennani N. Jeandel C. Lefebvre E. Blain H. Vidailhet M. Guéant J.L. Abnormal substrate levels that depend upon mitochondrial function in cerebrospinal fluid from Alzheimer patients Gerontology 1998 44 300 304 10.1159/000022031 9693263 · DOI
  32. [36]Parnetti L. Gaiti A. Polidori M.C. Brunetti M. Palumbo B. Chionne F. Cadini D. Cecchetti R. Senin U. Increased cerebrospinal fluid pyruvate levels in Alzheimer’s disease Neurosci. Lett. 1995 199 231 233 10.1016/0304-3940(95)12058-C 8577405 · DOI
  33. [37]Chen Y. Wang J. Cui C. Su Y. Jing D. Wu L. Liang P. Liang Z. Evaluating the association between brain atrophy, hypometabolism, and cognitive decline in Alzheimer’s disease: A PET/MRI study Aging 2021 13 7228 7246 10.18632/aging.202580 33640881 PMC7993730 · DOI
  34. [38]Marchitelli R. Aiello M. Cachia A. Quarantelli M. Cavaliere C. Postiglione A. Tedeschi G. Montella P. Milan G. Salvatore M. Simultaneous resting-state FDG-PET/fMRI in Alzheimer Disease: Relationship between glucose metabolism and intrinsic activity NeuroImage 2018 176 246 258 10.1016/j.neuroimage.2018.04.048 29709628 · DOI
  35. [39]La Joie R. Perrotin A. Barré L. Hommet C. Mézenge F. Ibazizene M. Camus V. Abbas A. Landeau B. Guilloteau D. Region-specific hierarchy between atrophy, hypometabolism, and β-amyloid (Aβ) load in Alzheimer’s disease dementia J. Neurosci. Off. J. Soc. Neurosci. 2012 32 16265 16273 10.1523/JNEUROSCI.2170-12.2012 PMC6794030 23152610 · DOI · Paper page
  36. [40]Schroeter M.L. Stein T. Maslowski N. Neumann J. Neural correlates of Alzheimer’s disease and mild cognitive impairment: A systematic and quantitative meta-analysis involving 1351 patients NeuroImage 2009 47 1196 1206 10.1016/j.neuroimage.2009.05.037 19463961 PMC2730171 · DOI
  37. [42]Buckner R.L. Snyder A.Z. Shannon B.J. LaRossa G. Sachs R. Fotenos A.F. Sheline Y.I. Klunk W.E. Mathis C.A. Morris J.C. Molecular, structural, and functional characterization of Alzheimer’s disease: Evidence for a relationship between default activity, amyloid, and memory J. Neurosci. Off. J. Soc. Neurosci. 2005 25 7709 7717 10.1523/JNEUROSCI.2177-05.2005 PMC6725245 16120771 · DOI · Paper page
  38. [43]Mullins R. Reiter D. Kapogiannis D. Magnetic resonance spectroscopy reveals abnormalities of glucose metabolism in the Alzheimer’s brain Ann. Clin. Transl. Neurol. 2018 5 262 272 10.1002/acn3.530 29560372 PMC5846391 · DOI
  39. [44]Chen L. Wei Z. Chan K.W. Li Y. Suchal K. Bi S. Huang J. Xu X. Wong P.C. Lu H. D-Glucose uptake and clearance in the tauopathy Alzheimer’s disease mouse brain detected by on-resonance variable delay multiple pulse MRI J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab. 2021 41 1013 1025 10.1177/0271678X20941264 PMC8054725 32669023 · DOI
  40. [48]Hoyer S. The effect of age on glucose and energy metabolism in brain cortex of rats Arch. Gerontol. Geriatr. 1985 4 193 203 10.1016/0167-4943(85)90001-9 4074019 · DOI
  41. [49]Alves V.S. Arcisio-Miranda M. Carrettiero D.C. Oliveira F.A. Transport of Glucose by the Plasma Membrane Affects the Removal and Concentration of Ca(2+) at Rest in Neurons—Implications of a Condition Prior to Alzheimer’s Disease? Neuroscience 2020 431 52 63 10.1016/j.neuroscience.2020.01.048 32058068 · DOI
  42. [50]Dong Y. Brewer G.J. Global Metabolic Shifts in Age and Alzheimer’s Disease Mouse Brains Pivot at NAD+/NADH Redox Sites J. Alzheimer’s Dis. 2019 71 119 140 10.3233/JAD-190408 31356210 PMC6839468 · DOI
  43. [51]Yudkoff M. Brain metabolism of branched-chain amino acids Glia 1997 21 92 98 10.1002/(SICI)1098-1136(199709)21:1<92::AID-GLIA10>3.0.CO;2-W 9298851 · DOI · Paper page
  44. [53]Nielsen J.E. Maltesen R.G. Havelund J.F. Færgeman N.J. Gotfredsen C.H. Vestergård K. Kristensen S.R. Pedersen S. Characterising Alzheimer’s disease through integrative NMR- and LC-MS-based metabolomics Metab. Open 2021 12 100125 10.1016/j.metop.2021.100125 PMC8479251 34622190 · DOI
  45. [54]Tynkkynen J. Chouraki V. van der Lee S.J. Hernesniemi J. Yang Q. Li S. Beiser A. Larson M.G. Sääksjärvi K. Shipley M.J. Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer’s disease: A prospective study in eight cohorts Alzheimer’s Dement. J. Alzheimer’s Assoc. 2018 14 723 733 10.1016/j.jalz.2018.01.003 29519576 PMC6082422 · DOI
  46. [55]Lipton S.A. Rosenberg P.A. Excitatory amino acids as a final common pathway for neurologic disorders N. Engl. J. Med. 1994 330 613 622 7905600
  47. [56]Choi D.W. Glutamate neurotoxicity and diseases of the nervous system Neuron 1988 1 623 634 10.1016/0896-6273(88)90162-6 2908446 · DOI
  48. [57]Hellman N.E. Gitlin J.D. Ceruloplasmin metabolism and function Annu. Rev. Nutr. 2002 22 439 458 10.1146/annurev.nutr.22.012502.114457 12055353 · DOI
  49. [58]Wang T. Xu S.F. Fan Y.G. Li L.B. Guo C. Iron Pathophysiology in Alzheimer’s Diseases Adv. Exp. Med. Biol. 2019 1173 67 104 31456206
  50. [59]Bush A.I. Copper, zinc, and the metallobiology of Alzheimer disease Alzheimer Dis. Assoc. Disord. 2003 17 147 150 10.1097/00002093-200307000-00005 14512827 · DOI
  51. [60]Ward R.J. Dexter D.T. Crichton R.R. Neurodegenerative diseases and therapeutic strategies using iron chelators J. Trace Elem. Med. Biol. Organ Soc. Miner. Trace Elem. 2015 31 267 273 10.1016/j.jtemb.2014.12.012 25716300 · DOI
  52. [61]Sparks D.L. Schreurs B.G. Trace amounts of copper in water induce beta-amyloid plaques and learning deficits in a rabbit model of Alzheimer’s disease Proc. Natl. Acad. Sci. USA 2003 100 11065 11069 10.1073/pnas.1832769100 12920183 PMC196927 · DOI
  53. [62]Fica-Contreras S.M. Shuster S.O. Durfee N.D. Bowe G.J.K. Henning N.J. Hill S.A. Vrla G.D. Stillman D.R. Suralik K.M. Sandwick R.K. Glycation of Lys-16 and Arg-5 in amyloid-β and the presence of Cu(2+) play a major role in the oxidative stress mechanism of Alzheimer’s disease J. Biol. Inorg. Chem. JBIC A Publ. Soc. Biol. Inorg. Chem. 2017 22 1211 1222 10.1007/s00775-017-1497-5 29038915 · DOI
  54. [63]Torsdottir G. Kristinsson J. Snaedal J. Jóhannesson T. Ceruloplasmin and iron proteins in the serum of patients with Alzheimer’s disease Dement. Geriatr. Cogn. Disord. Extra 2011 1 366 371 10.1159/000330467 22187543 PMC3243634 · DOI
  55. [64]Squitti R. Ghidoni R. Simonelli I. Ivanova I.D. Colabufo N.A. Zuin M. Benussi L. Binetti G. Cassetta E. Rongioletti M. Copper dyshomeostasis in Wilson disease and Alzheimer’s disease as shown by serum and urine copper indicators J. Trace Elem. Med. Biol. Organ Soc. Miner. Trace Elem. 2018 45 181 188 10.1016/j.jtemb.2017.11.005 29173477 · DOI
  56. [65]Kono S. Aceruloplasminemia: An update Int. Rev. Neurobiol. 2013 110 125 151 24209437
  57. [66]James S.A. Volitakis I. Adlard P.A. Duce J.A. Masters C.L. Cherny R.A. Bush A.I. Elevated labile Cu is associated with oxidative pathology in Alzheimer disease Free Radic. Biol. Med. 2012 52 298 302 10.1016/j.freeradbiomed.2011.10.446 22080049 · DOI
  58. [67]Tsvetkov P. Coy S. Petrova B. Dreishpoon M. Verma A. Abdusamad M. Rossen J. Joesch-Cohen L. Humeidi R. Spangler R.D. Copper induces cell death by targeting lipoylated TCA cycle proteins Science 2022 375 1254 1261 10.1126/science.abf0529 35298263 PMC9273333 · DOI · Paper page
  59. [68]Ayton S. Faux N.G. Bush A.I. Ferritin levels in the cerebrospinal fluid predict Alzheimer’s disease outcomes and are regulated by APOE Nat. Commun. 2015 6 6760 10.1038/ncomms7760 25988319 PMC4479012 · DOI
  60. [69]Damulina A. Pirpamer L. Soellradl M. Sackl M. Tinauer C. Hofer E. Enzinger C. Gesierich B. Duering M. Ropele S. Cross-sectional and Longitudinal Assessment of Brain Iron Level in Alzheimer Disease Using 3-T MRI Radiology 2020 296 619 626 10.1148/radiol.2020192541 32602825 · DOI
  61. [70]Ayton S. Wang Y. Diouf I. Schneider J.A. Brockman J. Morris M.C. Bush A.I. Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology Mol. Psychiatry 2020 25 2932 2941 10.1038/s41380-019-0375-7 30778133 PMC6698435 · DOI
  62. [71]Ayton S. Faux N.G. Bush A.I. Association of Cerebrospinal Fluid Ferritin Level with Preclinical Cognitive Decline in APOE-ε4 Carriers JAMA Neurol. 2017 74 122 125 10.1001/jamaneurol.2016.4406 27893873 · DOI
  63. [72]Ahmadi S. Zhu S. Sharma R. Wilson D.J. Kraatz H.B. Interaction of metal ions with tau protein. The case for a metal-mediated tau aggregation J. Inorg. Biochem. 2019 194 44 51 10.1016/j.jinorgbio.2019.02.007 30826589 · DOI
  64. [73]Bourassa M.W. Leskovjan A.C. Tappero R.V. Farquhar E.R. Colton C.A. Van Nostrand W.E. Miller L.M. Elevated copper in the amyloid plaques and iron in the cortex are observed in mouse models of Alzheimer’s disease that exhibit neurodegeneration Biomed. Spectrosc. Imaging 2013 2 129 139 10.3233/BSI-130041 24926425 PMC4051362 · DOI
  65. [74]Yan H.F. Zou T. Tuo Q.Z. Xu S. Li H. Belaidi A.A. Lei P. Ferroptosis: Mechanisms and links with diseases Signal Transduct. Target. Ther. 2021 6 49 10.1038/s41392-020-00428-9 33536413 PMC7858612 · DOI · Paper page
  66. [75]Wan L. Nie G. Zhang J. Luo Y. Zhang P. Zhang Z. Zhao B. β-Amyloid peptide increases levels of iron content and oxidative stress in human cell and Caenorhabditis elegans models of Alzheimer disease Free Radic. Biol. Med. 2011 50 122 129 10.1016/j.freeradbiomed.2010.10.707 21034809 · DOI
  67. [76]Freude S. Plum L. Schnitker J. Leeser U. Udelhoven M. Krone W. Bruning J.C. Schubert M. Peripheral hyperinsulinemia promotes tau phosphorylation in vivo Diabetes 2005 54 3343 3348 10.2337/diabetes.54.12.3343 16306348 · DOI
  68. [77]Kimura T. Ono T. Takamatsu J. Yamamoto H. Ikegami K. Kondo A. Hasegawa M. Ihara Y. Miyamoto E. Miyakawa T. Sequential changes of tau-site-specific phosphorylation during development of paired helical filaments Dementia 1996 7 177 181 10.1159/000106875 8835879 · DOI · Paper page
  69. [78]Tousoulis D. Antoniades C. Koumallos N. Stefanadis C. Pro-inflammatory cytokines in acute coronary syndromes: From bench to bedside Cytokine Growth Factor Rev. 2006 17 225 233 10.1016/j.cytogfr.2006.04.003 16750416 · DOI
  70. [79]Yarchoan M. Arnold S.E. Repurposing diabetes drugs for brain insulin resistance in Alzheimer disease Diabetes 2014 63 2253 2261 10.2337/db14-0287 24931035 PMC4066335 · DOI
  71. [80]Wilcox G. Insulin and insulin resistance Clin. Biochem. Rev. 2005 26 19 39 16278749 PMC1204764
  72. [81]Posner B.I. Insulin Signalling: The Inside Story Can. J. Diabetes 2017 41 108 113 10.1016/j.jcjd.2016.07.002 27614806 PMC5272803 · DOI
  73. [83]Yarza R. Vela S. Solas M. Ramirez M.J. c-Jun N-terminal Kinase (JNK) Signaling as a Therapeutic Target for Alzheimer’s Disease Front. Pharmacol. 2015 6 321 10.3389/fphar.2015.00321 26793112 PMC4709475 · DOI
  74. [84]Sabio G. Das M. Mora A. Zhang Z. Jun J.Y. Ko H.J. Barrett T. Kim J.K. Davis R.J. A stress signaling pathway in adipose tissue regulates hepatic insulin resistance Science 2008 322 1539 1543 10.1126/science.1160794 19056984 PMC2643026 · DOI · Paper page
  75. [85]Al-Salam A. Irwin D.M. Evolution of the vertebrate insulin receptor substrate (Irs) gene family BMC Evol. Biol. 2017 17 148 10.1186/s12862-017-0994-z 28645244 PMC5482937 · DOI
  76. [87]Yang L. Wang H. Liu L. Xie A. The Role of Insulin/IGF-1/PI3K/Akt/GSK3β Signaling in Parkinson’s Disease Dementia Front. Neurosci. 2018 12 73 10.3389/fnins.2018.00073 29515352 PMC5826217 · DOI
  77. [88]Cheng Z. Tseng Y. White M.F. Insulin signaling meets mitochondria in metabolism Trends Endocrinol. Metab. 2010 21 589 598 20638297 PMC3994704
  78. [89]Sonnenberg A. Tsou V.T. Müller A.D. The “institutional colon”: A frequent colonic dysmotility in psychiatric and neurologic disease Am. J. Gastroenterol. 1994 89 62 66 8273800
  79. [90]Silverstein J. Maclaren N. Riley W. Spillar R. Radjenovic D. Johnson S. Immunosuppression with azathioprine and prednisone in recent-onset insulin-dependent diabetes mellitus N. Engl. J. Med. 1988 319 599 604 10.1056/NEJM198809083191002 3045545 · DOI
  80. [91]Cox L.M. Blaser M.J. Antibiotics in early life and obesity Nat. Rev. Endocrinol. 2015 11 182 190 10.1038/nrendo.2014.210 25488483 PMC4487629 · DOI
  81. [92]O’Hara A.M. Shanahan F. The gut flora as a forgotten organ EMBO Rep. 2006 7 688 693 16819463 PMC1500832
  82. [93]Ley R.E. Peterson D.A. Gordon J.I. Ecological and evolutionary forces shaping microbial diversity in the human intestine Cell 2006 124 837 848 10.1016/j.cell.2006.02.017 16497592 · DOI · Paper page
  83. [94]Komaroff A.L. The Microbiome and Risk for Obesity and Diabetes JAMA 2017 317 355 356 10.1001/jama.2016.20099 28006047 · DOI
  84. [95]Qin J. Li R. Raes J. Arumugam M. Burgdorf K.S. Manichanh C. Nielsen T. Pons N. Levenez F. Yamada T. A human gut microbial gene catalogue established by metagenomic sequencing Nature 2010 464 59 65 10.1038/nature08821 20203603 PMC3779803 · DOI · Paper page
  85. [97]Seo D.O. Holtzman D.M. Gut Microbiota: From the Forgotten Organ to a Potential Key Player in the Pathology of Alzheimer’s Disease J. Gerontol. Ser. A Biol. Sci. Med. Sci. 2020 75 1232 1241 10.1093/gerona/glz262 31738402 PMC7302187 · DOI
  86. [98]Quigley E.M.M. Microbiota-Brain-Gut Axis and Neurodegenerative Diseases Curr. Neurol. Neurosci. Rep. 2017 17 94 10.1007/s11910-017-0802-6 29039142 · DOI · Paper page
  87. [99]Lin S.Y. Lin C.L. Wang I.K. Lin C.C. Lin C.H. Hsu W.H. Kao C.H. Dementia and vagotomy in Taiwan: A population-based cohort study BMJ Open 2018 8 e019582 10.1136/bmjopen-2017-019582 PMC5884346 29602843 · DOI
  88. [100]Soscia S.J. Kirby J.E. Washicosky K.J. Tucker S.M. Ingelsson M. Hyman B. Burton M.A. Goldstein L.E. Duong S. Tanzi R.E. The Alzheimer’s disease-associated amyloid beta-protein is an antimicrobial peptide PLoS ONE 2010 5 e9505 10.1371/journal.pone.0009505 20209079 PMC2831066 · DOI · Paper page
  89. [101]Sun Y. Sommerville N.R. Liu J.Y.H. Ngan M.P. Poon D. Ponomarev E.D. Lu Z. Kung J.S.C. Rudd J.A. Intra-gastrointestinal amyloid-β1-42 oligomers perturb enteric function and induce Alzheimer’s disease pathology J. Physiol. 2020 598 4209 4223 10.1113/JP279919 32617993 PMC7586845 · DOI
  90. [102]Vogt N.M. Kerby R.L. Dill-McFarland K.A. Harding S.J. Merluzzi A.P. Johnson S.C. Carlsson C.M. Asthana S. Zetterberg H. Blennow K. Gut microbiome alterations in Alzheimer’s disease Sci. Rep. 2017 7 13537 10.1038/s41598-017-13601-y 29051531 PMC5648830 · DOI · Paper page
  91. [103]Roy Sarkar S. Banerjee S. Gut microbiota in neurodegenerative disorders J. Neuroimmunol. 2019 328 98 104 10.1016/j.jneuroim.2019.01.004 30658292 · DOI
  92. [104]Li J. Zhou H. Fu X. Zhang M. Sun F. Fan H. Dynamic role of macrophage CX3CR1 expression in inflammatory bowel disease Immunol. Lett. 2021 232 39 44 33582183
  93. [105]Fung T.C. Olson C.A. Hsiao E.Y. Interactions between the microbiota, immune and nervous systems in health and disease Nat. Neurosci. 2017 20 145 155 10.1038/nn.4476 28092661 PMC6960010 · DOI · Paper page
  94. [108]Krasemann S. Madore C. Cialic R. Baufeld C. Calcagno N. El Fatimy R. Beckers L. O’Loughlin E. Xu Y. Fanek Z. The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases Immunity 2017 47 566 581.e9 28930663 PMC5719893
  95. [109]Bélanger M. Allaman I. Magistretti P.J. Brain energy metabolism: Focus on astrocyte-neuron metabolic cooperation Cell Metab. 2011 14 724 738 22152301
  96. [110]Mookerjee S.A. Gerencser A.A. Nicholls D.G. Brand M.D. Quantifying intracellular rates of glycolytic and oxidative ATP production and consumption using extracellular flux measurements J. Biol. Chem. 2017 292 7189 7207 10.1074/jbc.M116.774471 28270511 PMC5409486 · DOI
  97. [111]Pietrocola F. Galluzzi L. Bravo-San Pedro J.M. Madeo F. Kroemer G. Acetyl coenzyme A: A central metabolite and second messenger Cell Metab. 2015 21 805 821 10.1016/j.cmet.2015.05.014 26039447 · DOI
  98. [112]Vacanti N.M. Divakaruni A.S. Green C.R. Parker S.J. Henry R.R. Ciaraldi T.P. Murphy A.N. Metallo C.M. Regulation of substrate utilization by the mitochondrial pyruvate carrier Mol. Cell 2014 56 425 435 10.1016/j.molcel.2014.09.024 25458843 PMC4267523 · DOI · Paper page
  99. [113]Guo R. Zong S. Wu M. Gu J. Yang M. Architecture of Human Mitochondrial Respiratory Megacomplex I(2)III(2)IV(2) Cell 2017 170 1247 1257.e12 10.1016/j.cell.2017.07.050 28844695 · DOI
  100. [114]Hüttemann M. Lee I. Pecinova A. Pecina P. Przyklenk K. Doan J.W. Regulation of oxidative phosphorylation, the mitochondrial membrane potential, and their role in human disease J. Bioenerg. Biomembr. 2008 40 445 456 10.1007/s10863-008-9169-3 18843528 · DOI
  101. [115]Brand M.D. Nicholls D.G. Assessing mitochondrial dysfunction in cells Biochem. J. 2011 435 297 312 10.1042/BJ20110162 21726199 PMC3076726 · DOI
  102. [116]Orrenius S. Zhivotovsky B. Nicotera P. Regulation of cell death: The calcium-apoptosis link. Nature reviews Mol. Cell Biol. 2003 4 552 565 12838338
  103. [117]Swerdlow R.H. Khan S.M. A “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease Med. Hypotheses 2004 63 8 20 10.1016/j.mehy.2003.12.045 15193340 · DOI · Paper page
  104. [118]McGeer P.L. Rogers J. Anti-inflammatory agents as a therapeutic approach to Alzheimer’s disease Neurology 1992 42 447 449 10.1212/WNL.42.2.447 1736183 · DOI
  105. [119]Sorrentino V. Romani M. Mouchiroud L. Beck J.S. Zhang H. D’Amico D. Moullan N. Potenza F. Schmid A.W. Rietsch S. Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity Nature 2017 552 187 193 10.1038/nature25143 29211722 PMC5730497 · DOI · Paper page
  106. [121]Chandel N.S. Evolution of Mitochondria as Signaling Organelles Cell Metab. 2015 22 204 206 10.1016/j.cmet.2015.05.013 26073494 · DOI · Paper page
  107. [123]Brand M.D. Chien L.F. Ainscow E.K. Rolfe D.F. Porter R.K. The causes and functions of mitochondrial proton leak Biochim. Biophys. Acta 1994 1187 132 139 10.1016/0005-2728(94)90099-X 8075107 · DOI · Paper page
  108. [125]Weinberg S.E. Singer B.D. Steinert E.M. Martinez C.A. Mehta M.M. Martínez-Reyes I. Gao P. Helmin K.A. Abdala-Valencia H. Sena L.A. Mitochondrial complex III is essential for suppressive function of regulatory T cells Nature 2019 565 495 499 10.1038/s41586-018-0846-z 30626970 PMC6345596 · DOI
  109. [126]Campbell S.L. Wellen K.E. Metabolic Signaling to the Nucleus in Cancer Mol. Cell 2018 71 398 408 10.1016/j.molcel.2018.07.015 30075141 · DOI
  110. [127]Gupta R. Ambasta R.K. Kumar P. Multifaced role of protein deacetylase sirtuins in neurodegenerative disease Neurosci. Biobehav. Rev. 2022 132 976 997 10.1016/j.neubiorev.2021.10.047 34742724 · DOI
  111. [128]Katsyuba E. Auwerx J. Modulating NAD(+) metabolism, from bench to bedside EMBO J. 2017 36 2670 2683 10.15252/embj.201797135 28784597 PMC5599801 · DOI
  112. [129]Verdin E. NAD+ in aging, metabolism, and neurodegeneration Science 2015 350 1208 1213 10.1126/science.aac4854 26785480 · DOI · Paper page
  113. [130]van de Ven R.A.H. Santos D. Haigis M.C. Mitochondrial Sirtuins and Molecular Mechanisms of Aging Trends Mol. Med. 2017 23 320 331 10.1016/j.molmed.2017.02.005 28285806 PMC5713479 · DOI
  114. [132]Ruderman N.B. Xu X.J. Nelson L. Cacicedo J.M. Saha A.K. Lan F. Ido Y. AMPK and SIRT1: A long-standing partnership? American journal of physiology Endocrinol. Metab. 2010 298 E751 E760 PMC2853213 20103737
  115. [134]West A.P. Khoury-Hanold W. Staron M. Tal M.C. Pineda C.M. Lang S.M. Bestwick M. Duguay B.A. Raimundo N. MacDuff D.A. Mitochondrial DNA stress primes the antiviral innate immune response Nature 2015 520 553 557 10.1038/nature14156 25642965 PMC4409480 · DOI · Paper page
  116. [135]López-Crisosto C. Bravo-Sagua R. Rodriguez-Peña M. Mera C. Castro P.F. Quest A.F. Rothermel B.A. Cifuentes M. Lavandero S. ER-to-mitochondria miscommunication and metabolic diseases Biochim. Biophys. Acta 2015 1852 Pt A 2096 2105 10.1016/j.bbadis.2015.07.011 26171812 · DOI
  117. [136]Flannery P.J. Trushina E. Mitochondrial dynamics and transport in Alzheimer’s disease Mol. Cell. Neurosci. 2019 98 109 120 10.1016/j.mcn.2019.06.009 31216425 PMC6614006 · DOI
  118. [137]Labbé K. Murley A. Nunnari J. Determinants and functions of mitochondrial behavior Annu. Rev. Cell Dev. Biol. 2014 30 357 391 10.1146/annurev-cellbio-101011-155756 25288115 · DOI
  119. [138]Zhu L. Zhou Q. He L. Chen L. Mitochondrial unfolded protein response: An emerging pathway in human diseases Free Radic. Biol. Med. 2021 163 125 134 10.1016/j.freeradbiomed.2020.12.013 33347985 · DOI
  120. [140]Yin W. Signore A.P. Iwai M. Cao G. Gao Y. Chen J. Rapidly increased neuronal mitochondrial biogenesis after hypoxic-ischemic brain injury Stroke 2008 39 3057 3063 10.1161/STROKEAHA.108.520114 18723421 PMC2726706 · DOI
  121. [141]Baker N. Wade S. Triolo M. Girgis J. Chwastek D. Larrigan S. Feige P. Fujita R. Crist C. Rudnicki M.A. The mitochondrial protein OPA1 regulates the quiescent state of adult muscle stem cells Cell Stem Cell 2022 29 1315 1332.e9 10.1016/j.stem.2022.07.010 35998642 PMC10249109 · DOI
  122. [142]Bertholet A.M. Delerue T. Millet A.M. Moulis M.F. David C. Daloyau M. Arnauné-Pelloquin L. Davezac N. Mils V. Miquel M.C. Mitochondrial fusion/fission dynamics in neurodegeneration and neuronal plasticity Neurobiol. Dis. 2016 90 3 19 10.1016/j.nbd.2015.10.011 26494254 · DOI · Paper page
  123. [143]Stojanovski D. Koutsopoulos O.S. Okamoto K. Ryan M.T. Levels of human Fis1 at the mitochondrial outer membrane regulate mitochondrial morphology J. Cell Sci. 2004 117 Pt 7 1201 1210 10.1242/jcs.01058 14996942 · DOI
  124. [145]Pitts K.R. Yoon Y. Krueger E.W. McNiven M.A. The dynamin-like protein DLP1 is essential for normal distribution and morphology of the endoplasmic reticulum and mitochondria in mammalian cells Mol. Biol. Cell 1999 10 4403 4417 10.1091/mbc.10.12.4403 10588666 PMC25766 · DOI
  125. [146]Kim D.I. Lee K.H. Gabr A.A. Choi G.E. Kim J.S. Ko S.H. Han H.J. Aβ-Induced Drp1 phosphorylation through Akt activation promotes excessive mitochondrial fission leading to neuronal apoptosis Biochim. Biophys. Acta 2016 1863 2820 2834 10.1016/j.bbamcr.2016.09.003 27599716 · DOI
  126. [148]Zorova L.D. Popkov V.A. Plotnikov E.Y. Silachev D.N. Pevzner I.B. Jankauskas S.S. Babenko V.A. Zorov S.D. Balakireva A.V. Juhaszova M. Mitochondrial membrane potential Anal. Biochem. 2018 552 50 59 10.1016/j.ab.2017.07.009 28711444 PMC5792320 · DOI
  127. [150]Jeong Y.Y. Han S. Jia N. Zhang M. Sheshadri P. Tammineni P. Cheung J. Nissenbaum M. Baskar S.S. Kwan K. Broad activation of the Parkin pathway induces synaptic mitochondrial deficits in early tauopathy Brain A J. Neurol. 2022 145 305 323 10.1093/brain/awab243 PMC8967101 35022692 · DOI
  128. [151]Kerr J.S. Adriaanse B.A. Greig N.H. Mattson M.P. Cader M.Z. Bohr V.A. Fang E.F. Mitophagy and Alzheimer’s Disease: Cellular and Molecular Mechanisms Trends Neurosci. 2017 40 151 166 10.1016/j.tins.2017.01.002 28190529 PMC5341618 · DOI · Paper page
  129. [152]Kobro-Flatmoen A. Lagartos-Donate M.J. Aman Y. Edison P. Witter M.P. Fang E.F. Re-emphasizing early Alzheimer’s disease pathology starting in select entorhinal neurons, with a special focus on mitophagy Ageing Res. Rev. 2021 67 101307 10.1016/j.arr.2021.101307 33621703 · DOI · Paper page
  130. [154]Lampinen R. Belaya I. Saveleva L. Liddell J.R. Rait D. Huuskonen M.T. Giniatullina R. Sorvari A. Soppela L. Mikhailov N. Neuron-astrocyte transmitophagy is altered in Alzheimer’s disease Neurobiol. Dis. 2022 170 105753 10.1016/j.nbd.2022.105753 35569719 · DOI · Paper page
  131. [155]Bordt E.A. Clerc P. Roelofs B.A. Saladino A.J. Tretter L. Adam-Vizi V. Cherok E. Khalil A. Yadava N. Ge S.X. The Putative Drp1 Inhibitor mdivi-1 Is a Reversible Mitochondrial Complex I Inhibitor that Modulates Reactive Oxygen Species Dev. Cell 2017 40 583 594.e6 10.1016/j.devcel.2017.02.020 28350990 PMC5398851 · DOI
  132. [156]Wang W. Yin J. Ma X. Zhao F. Siedlak S.L. Wang Z. Torres S. Fujioka H. Xu Y. Perry G. Inhibition of mitochondrial fragmentation protects against Alzheimer’s disease in rodent model Hum. Mol. Genet. 2017 26 4118 4131 10.1093/hmg/ddx299 28973308 PMC5886251 · DOI · Paper page
  133. [157]Yang Y. Liu Y. Zhu J. Song S. Huang Y. Zhang W. Sun Y. Hao J. Yang X. Gao Q. Neuroinflammation-mediated mitochondrial dysregulation involved in postoperative cognitive dysfunction Free Radic. Biol. Med. 2022 178 134 146 10.1016/j.freeradbiomed.2021.12.004 34875338 · DOI
  134. [158]Rege S.D. Geetha T. Griffin G.D. Broderick T.L. Babu J.R. Neuroprotective effects of resveratrol in Alzheimer disease pathology Front. Aging Neurosci. 2014 6 218 10.3389/fnagi.2014.00218 25309423 PMC4161050 · DOI
  135. [159]Chen Y. Zhang H. Ji S. Jia P. Chen Y. Li Y. Wang T. Resveratrol and its derivative pterostilbene attenuate oxidative stress-induced intestinal injury by improving mitochondrial redox homeostasis and function via SIRT1 signaling Free Radic. Biol. Med. 2021 177 1 14 10.1016/j.freeradbiomed.2021.10.011 34648904 · DOI
  136. [160]Hubbard B.P. Sinclair D.A. Small molecule SIRT1 activators for the treatment of aging and age-related diseases Trends Pharmacol. Sci. 2014 35 146 154 10.1016/j.tips.2013.12.004 24439680 PMC3970218 · DOI
  137. [161]Tellone E. Galtieri A. Russo A. Giardina B. Ficarra S. Resveratrol: A Focus on Several Neurodegenerative Diseases Oxidative Med. Cell. Longev. 2015 2015 392169 10.1155/2015/392169 PMC4477222 26180587 · DOI
  138. [162]Witte A.V. Kerti L. Margulies D.S. Flöel A. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults J. Neurosci. Off. J. Soc. Neurosci. 2014 34 7862 7870 10.1523/JNEUROSCI.0385-14.2014 PMC6608268 24899709 · DOI · Paper page
  139. [163]Sadovnikova I.S. Gureev A.P. Ignatyeva D.A. Gryaznova M.V. Chernyshova E.V. Krutskikh E.P. Novikova A.G. Popov V.N. Nrf2/ARE Activators Improve Memory in Aged Mice via Maintaining of Mitochondrial Quality Control of Brain and the Modulation of Gut Microbiome Pharmaceuticals 2021 14 607 10.3390/ph14070607 34201885 PMC8308546 · DOI
  140. [164]Zhang L. Zhang S. Maezawa I. Trushin S. Minhas P. Pinto M. Jin L.W. Prasain K. Nguyen T.D. Yamazaki Y. Modulation of mitochondrial complex I activity averts cognitive decline in multiple animal models of familial Alzheimer’s Disease EBioMedicine 2015 2 294 305 Erratum in EBioMedicine 2019, 42, 532 10.1016/j.ebiom.2015.03.009 26086035 PMC4465115 · DOI
  141. [165]Stojakovic A. Trushin S. Sheu A. Khalili L. Chang S.Y. Li X. Christensen T. Salisbury J.L. Geroux R.E. Gateno B. Partial inhibition of mitochondrial complex I ameliorates Alzheimer’s disease pathology and cognition in APP/PS1 female mice Commun. Biol. 2021 4 61 10.1038/s42003-020-01584-y 33420340 PMC7794523 · DOI · Paper page
  142. [166]Stojakovic A. Chang S.Y. Nesbitt J. Pichurin N.P. Ostroot M.A. Aikawa T. Kanekiyo T. Trushina E. Partial Inhibition of Mitochondrial Complex I Reduces Tau Pathology and Improves Energy Homeostasis and Synaptic Function in 3xTg-AD Mice J. Alzheimer’s Dis. 2021 79 335 353 33285637 PMC7902954
  143. [167]Maezawa I. Hong H.S. Wu H.C. Battina S.K. Rana S. Iwamoto T. Radke G.A. Pettersson E. Martin G.M. Hua D.H. A novel tricyclic pyrone compound ameliorates cell death associated with intracellular amyloid-beta oligomeric complexes J. Neurochem. 2006 98 57 67 10.1111/j.1471-4159.2006.03862.x 16805796 · DOI
  144. [168]Choi S.W. Gerencser A.A. Nicholls D.G. Bioenergetic analysis of isolated cerebrocortical nerve terminals on a microgram scale: Spare respiratory capacity and stochastic mitochondrial failure J. Neurochem. 2009 109 1179 1191 10.1111/j.1471-4159.2009.06055.x 19519782 PMC2696043 · DOI
  145. [169]Bailey C.J. Turner R.C. Metformin N. Engl. J. Med. 1996 334 574 579 10.1056/NEJM199602293340906 8569826 · DOI · Paper page
  146. [170]Foretz M. Guigas B. Bertrand L. Pollak M. Viollet B. Metformin: From mechanisms of action to therapies Cell Metab. 2014 20 953 966 10.1016/j.cmet.2014.09.018 25456737 · DOI · Paper page
  147. [172]Tumminia A. Vinciguerra F. Parisi M. Frittitta L. Type 2 Diabetes Mellitus and Alzheimer’s Disease: Role of Insulin Signalling and Therapeutic Implications Int. J. Mol. Sci. 2018 19 3306 10.3390/ijms19113306 30355995 PMC6275025 · DOI
  148. [173]Kickstein E. Krauss S. Thornhill P. Rutschow D. Zeller R. Sharkey J. Williamson R. Fuchs M. Köhler A. Glossmann H. Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling Proc. Natl. Acad. Sci. USA 2010 107 21830 21835 10.1073/pnas.0912793107 21098287 PMC3003072 · DOI
  149. [174]Chen Y. Zhao S. Fan Z. Li Z. Zhu Y. Shen T. Li K. Yan Y. Tian J. Liu Z. Metformin attenuates plaque-associated tau pathology and reduces amyloid-β burden in APP/PS1 mice Alzheimer’s Res. Ther. 2021 13 40 10.1186/s13195-020-00761-9 33563332 PMC7871393 · DOI · Paper page
  150. [175]Oliveira W.H. Nunes A.K. França M.E. Santos L.A. Lós D.B. Rocha S.W. Barbosa K.P. Rodrigues G.B. Peixoto C.A. Effects of metformin on inflammation and short-term memory in streptozotocin-induced diabetic mice Brain Res. 2016 1644 149 160 10.1016/j.brainres.2016.05.013 27174003 · DOI
  151. [177]Li C.Y. Kuo C.L. Chang Y.H. Lu C.L. Martini S. Hou W.H. Association Between Trajectory of Severe Hypoglycemia and Dementia in Patients With Type 2 Diabetes: A Population-based Study J. Epidemiol. 2022 32 423 430 10.2188/jea.JE20200518 33678721 PMC9359896 · DOI
  152. [179]Dunkley A.J. Fitzpatrick C. Gray L.J. Waheed G. Heller S.R. Frier B.M. Davies M.J. Khunti K. Incidence and severity of hypoglycaemia in type 2 diabetes by treatment regimen: A UK multisite 12-month prospective observational study Diabetes Obes. Metab. 2019 21 1585 1595 10.1111/dom.13690 30843327 · DOI
  153. [180]Orkaby A.R. Cho K. Cormack J. Gagnon D.R. Driver J.A. Metformin vs sulfonylurea use and risk of dementia in US veterans aged ≥65 years with diabetes Neurology 2017 89 1877 1885 10.1212/WNL.0000000000004586 28954880 PMC5664297 · DOI
  154. [181]Hsu C.C. Wahlqvist M.L. Lee M.S. Tsai H.N. Incidence of dementia is increased in type 2 diabetes and reduced by the use of sulfonylureas and metformin J. Alzheimer’s Dis. 2011 24 485 493 10.3233/JAD-2011-101524 21297276 · DOI · Paper page
  155. [182]Herath P.M. Cherbuin N. Eramudugolla R. Anstey K.J. The Effect of Diabetes Medication on Cognitive Function: Evidence from the PATH Through Life Study BioMed Res. Int. 2016 2016 7208429 10.1155/2016/7208429 27195294 PMC4853928 · DOI
  156. [185]Wang T. Kuang W. Chen W. Xu W. Zhang L. Li Y. Li H. Peng Y. Chen Y. Wang B. A phase II randomized trial of sodium oligomannate in Alzheimer’s dementia Alzheimer’s Res. Ther. 2020 12 110 10.1186/s13195-020-00678-3 32928279 PMC7489025 · DOI · Paper page
  157. [187]McLachlan D.R. Smith W.L. Kruck T.P. Desferrioxamine and Alzheimer’s disease: Video home behavior assessment of clinical course and measures of brain aluminum Ther. Drug Monit. 1993 15 602 607 10.1097/00007691-199312000-00027 8122302 · DOI
  158. [188]Fine J.M. Forsberg A.C. Stroebel B.M. Faltesek K.A. Verden D.R. Hamel K.A. Raney E.B. Crow J.M. Haase L.R. Knutzen K.E. Intranasal deferoxamine affects memory loss, oxidation, and the insulin pathway in the streptozotocin rat model of Alzheimer’s disease J. Neurol. Sci. 2017 380 164 171 10.1016/j.jns.2017.07.028 28870559 · DOI
  159. [189]Zhang Y. He M.L. Deferoxamine enhances alternative activation of microglia and inhibits amyloid beta deposits in APP/PS1 mice Brain Res. 2017 1677 86 92 10.1016/j.brainres.2017.09.019 28963052 · DOI
  160. [190]Rao S.S. Portbury S.D. Lago L. McColl G. Finkelstein D.I. Bush A.I. Adlard P.A. The Iron Chelator Deferiprone Improves the Phenotype in a Mouse Model of Tauopathy J. Alzheimer’s Dis. 2020 77 753 771 10.3233/JAD-200551 32741833 · DOI
  161. [192]Faux N.G. Ritchie C.W. Gunn A. Rembach A. Tsatsanis A. Bedo J. Harrison J. Lannfelt L. Blennow K. Zetterberg H. PBT2 rapidly improves cognition in Alzheimer’s Disease: Additional phase II analyses J. Alzheimer’s Dis. 2010 20 509 516 10.3233/JAD-2010-1390 20164561 · DOI
  162. [193]Galatti L. Giustini S.E. Sessa A. Polimeni G. Salvo F. Spina E. Caputi A.P. Neuropsychiatric reactions to drugs: An analysis of spontaneous reports from general practitioners in Italy Pharmacol. Res. 2005 51 211 216 10.1016/j.phrs.2004.08.003 15661570 · DOI
  163. [194]Adlard P.A. Bica L. White A.R. Nurjono M. Filiz G. Crouch P.J. Donnelly P.S. Cappai R. Finkelstein D.I. Bush A.I. Metal ionophore treatment restores dendritic spine density and synaptic protein levels in a mouse model of Alzheimer’s disease PLoS ONE 2011 6 e17669 10.1371/journal.pone.0017669 21412423 PMC3055881 · DOI
  164. [195]Crouch P.J. Savva M.S. Hung L.W. Donnelly P.S. Mot A.I. Parker S.J. Greenough M.A. Volitakis I. Adlard P.A. Cherny R.A. The Alzheimer’s therapeutic PBT2 promotes amyloid-β degradation and GSK3 phosphorylation via a metal chaperone activity J. Neurochem. 2011 119 220 230 10.1111/j.1471-4159.2011.07402.x 21797865 · DOI
  165. [196]Lannfelt L. Blennow K. Zetterberg H. Batsman S. Ames D. Harrison J. Masters C.L. Targum S. Bush A.I. Murdoch R. Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer’s disease: A phase IIa, double-blind, randomised, placebo-controlled trial. The Lancet Neurology 2008 7 779 786 18672400
  166. [197]Villemagne V.L. Rowe C.C. Barnham K.J. Cherny R. Woodward M. Bozinosvski S. Salvado O. Bourgeat P. Perez K. Fowler C. A randomized, exploratory molecular imaging study targeting amyloid β with a novel 8-OH quinoline in Alzheimer’s disease: The PBT2-204 IMAGINE study Alzheimer’s Dement. 2017 3 622 635 10.1016/j.trci.2017.10.001 PMC5702880 29201996 · DOI
  167. [200]Wilkins H.M. Swerdlow R.H. Mitochondrial links between brain aging and Alzheimer’s disease Transl. Neurodegener. 2021 10 33 10.1186/s40035-021-00261-2 34465385 PMC8408998 · DOI
  168. [201]Wang Y. Oxer D. Hekimi S. Mitochondrial function and lifespan of mice with controlled ubiquinone biosynthesis Nat. Commun. 2015 6 6393 10.1038/ncomms7393 25744659 PMC4715896 · DOI
  169. [204]Lapointe J. Wang Y. Bigras E. Hekimi S. The submitochondrial distribution of ubiquinone affects respiration in long-lived Mclk1+/- mice J. Cell Biol. 2012 199 215 224 10.1083/jcb.201203090 23045551 PMC3471228 · DOI
  170. [205]Yang W. Hekimi S. Two modes of mitochondrial dysfunction lead independently to lifespan extension in Caenorhabditis elegans Aging Cell 2010 9 433 447 10.1111/j.1474-9726.2010.00571.x 20346072 · DOI
  171. [206]Copeland J.M. Cho J. Lo T. Jr. Hur J.H. Bahadorani S. Arabyan T. Rabie J. Soh J. Walker D.W. Extension of Drosophila life span by RNAi of the mitochondrial respiratory chain Curr. Biol. CB 2009 19 1591 1598 10.1016/j.cub.2009.08.016 19747824 · DOI · Paper page
  172. [207]Lapointe J. Hekimi S. Early mitochondrial dysfunction in long-lived Mclk1+/− mice J. Biol. Chem. 2008 283 26217 26227 10.1074/jbc.M803287200 18635541 PMC3258865 · DOI
  173. [208]Kayser E.B. Sedensky M.M. Morgan P.G. Hoppel C.L. Mitochondrial oxidative phosphorylation is defective in the long-lived mutant clk-1 J. Biol. Chem. 2004 279 54479 54486 10.1074/jbc.M403066200 15269213 · DOI
  174. [209]Baumgart M. Priebe S. Groth M. Hartmann N. Menzel U. Pandolfini L. Koch P. Felder M. Ristow M. Englert C. Longitudinal RNA-Seq Analysis of Vertebrate Aging Identifies Mitochondrial Complex I as a Small-Molecule-Sensitive Modifier of Lifespan Cell Syst. 2016 2 122 132 10.1016/j.cels.2016.01.014 27135165 · DOI

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Authors
Song, M., & Fan, X.
Affiliations
Zhejiang Chinese Medical University (CN)
Corresponding author
Fan, Xiang
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2023-05-07
Volume
24
Issue
9
Pages
8398
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms24098398
PMC
PMC10179273
OpenAlex
W4376630572
Cited by
11
References
34
Citations by year
2026: 3 · 2025: 4 · 2024: 3 · 2023: 1
FWCI
0.37
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (82174047, 81622051)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, systemic metabolism, mitochondria, integrated stress response, mitochondrial bioenergetics, mitochondrial quality control, neuroinflammation, aging, gut microbiota, therapeutic target, healthy aging, neuroprotection
MeSH terms
Aged, Aging, Alzheimer Disease, Energy Metabolism, Humans, Mitochondria, Oxidative Stress

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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