Skip to content
2000
Volume 20, Issue 7
  • ISSN: 1574-8855
  • E-ISSN: 2212-3903

Abstract

Alzheimer's Disease (AD) is a common neurodegenerative disease caused by the gradual degradation of neurons. Current therapies for AD primarily relieve symptoms. However, a comprehensive understanding of the fundamental processes of AD progression is still lacking. Mitochondrial dysfunction is a central factor in the etiology of AD. Numerous studies have shown that mitochondrial function is severely impaired during the development of AD. There has been much interest in preliminary research on the different treatment methods for mitochondrial dysfunction. Nonetheless, clinical trials have shown little progress to date. This article aims to review the various aspects of the changes in mitochondrial dynamics observed in Alzheimer's, which may impact the progression of this severe condition. Furthermore, we investigated therapeutic approaches that aim to enhance mitochondrial dynamics and function, potentially providing a different approach to overcome the limitations of amyloid-directed therapy.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cdth/10.2174/0115748855291425240802100148
2024-08-12
2025-12-03

  • From This Site

    /content/journals/cdth/10.2174/0115748855291425240802100148
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. CoyleJ.T. PriceD.L. DeLongM.R. Alzheimer’s disease: a disorder of cortical cholinergic innervation.Science198321945891184119010.1126/science.63385896338589
     [Google Scholar]
  2. SelkoeD.J. Alzheimer’s disease: genes, proteins, and therapy.Physiol. Rev.200181274176610.1152/physrev.2001.81.2.74111274343
     [Google Scholar]
  3. FeiginV.L. NicholsE. AlamT. BannickM.S. BeghiE. BlakeN. CulpepperW.J. DorseyE.R. ElbazA. EllenbogenR.G. FisherJ.L. FitzmauriceC. GiussaniG. GlennieL. JamesS.L. JohnsonC.O. KassebaumN.J. LogroscinoG. MarinB. Mountjoy-VenningW.C. NguyenM. Ofori-AsensoR. PatelA.P. PiccininniM. RothG.A. SteinerT.J. StovnerL.J. SzoekeC.E.I. TheadomA. VollsetS.E. WallinM.T. WrightC. ZuntJ.R. AbbasiN. Abd-AllahF. AbdelalimA. AbdollahpourI. AboyansV. AbrahaH.N. AcharyaD. AdamuA.A. AdebayoO.M. AdeoyeA.M. AdsuarJ.C. AfaridehM. AgrawalS. AhmadiA. AhmedM.B. AichourA.N. AichourI. AichourM.T.E. AkinyemiR.O. AkseerN. Al-EyadhyA. Al-Shahi SalmanR. AlahdabF. AleneK.A. AljunidS.M. AltirkawiK. Alvis-GuzmanN. AnberN.H. AntonioC.A.T. ArablooJ. AremuO. ÄrnlövJ. AsayeshH. AsgharR.J. AtalayH.T. AwasthiA. Ayala QuintanillaB.P. AyukT.B. BadawiA. BanachM. BanoubJ.A.M. BarbozaM.A. Barker-ColloS.L. BärnighausenT.W. BauneB.T. BediN. BehzadifarM. BehzadifarM. BéjotY. BekeleB.B. BelachewA.B. BennettD.A. BensenorI.M. BerhaneA. BeuranM. BhattacharyyaK. BhuttaZ.A. BiadgoB. BijaniA. BililignN. Bin SayeedM.S. BlazesC.K. BrayneC. ButtZ.A. Campos-NonatoI.R. Cantu-BritoC. CarM. CárdenasR. CarreroJ.J. CarvalhoF. Castañeda-OrjuelaC.A. CastroF. Catalá-LópezF. CerinE. ChaiahY. ChangJ-C. ChatziralliI. ChiangP.P-C. ChristensenH. ChristopherD.J. CooperC. CortesiP.A. CostaV.M. CriquiM.H. CroweC.S. DamascenoA.A.M. DaryaniA. De la Cruz-GóngoraV. De la HozF.P. De LeoD. DemozG.T. DeribeK. DharmaratneS.D. DiazD. DinberuM.T. DjalaliniaS. DokuD.T. DubeyM. DubljaninE. DukenE.E. EdvardssonD. El-KhatibZ. EndresM. EndriesA.Y. EskandariehS. EsteghamatiA. EsteghamatiS. FarhadiF. FaroA. FarzadfarF. FarzaeiM.H. FatimaB. FereshtehnejadS-M. FernandesE. FeyissaG.T. FilipI. FischerF. FukumotoT. GanjiM. GankpeF.G. Garcia-GordilloM.A. GebreA.K. GebremichaelT.G. GelawB.K. GeleijnseJ.M. GeremewD. GezaeK.E. Ghasemi-KasmanM. GideyM.Y. GillP.S. GillT.K. GirmaE.T. GnedovskayaE.V. GoulartA.C. GradaA. GrossoG. GuoY. GuptaR. GuptaR. HaagsmaJ.A. HagosT.B. Haj-MirzaianA. Haj-MirzaianA. HamadehR.R. HamidiS. HankeyG.J. HaoY. HaroJ.M. HassankhaniH. HassenH.Y. HavmoellerR. HayS.I. HegazyM.I. HeidariB. HenokA. HeydarpourF. HoangC.L. HoleM.K. Homaie RadE. HosseiniS.M. HuG. IgumborE.U. IlesanmiO.S. IrvaniS.S.N. IslamS.M.S. JakovljevicM. JavanbakhtM. JhaR.P. JobanputraY.B. JonasJ.B. JozwiakJ.J. JürissonM. KahsayA. KalaniR. KalkondeY. KamilT.A. KanchanT. KaramiM. KarchA. KarimiN. KasaeianA. KassaT.D. KassaZ.Y. KaulA. KefaleA.T. KeiyoroP.N. KhaderY.S. KhafaieM.A. KhalilI.A. KhanE.A. KhangY-H. KhazaieH. KiadaliriA.A. KiirithioD.N. KimA.S. KimD. KimY-E. KimY.J. KisaA. KokuboY. KoyanagiA. KrishnamurthiR.V. Kuate DefoB. Kucuk BicerB. KumarM. LaceyB. LafranconiA. LansinghV.C. LatifiA. LeshargieC.T. LiS. LiaoY. LinnS. LoW.D. LopezJ.C.F. LorkowskiS. LotufoP.A. LucasR.M. LuneviciusR. MackayM.T. MahotraN.B. MajdanM. MajdzadehR. MajeedA. MalekzadehR. MaltaD.C. ManafiN. MansourniaM.A. MantovaniL.G. MärzW. Mashamba-ThompsonT.P. MassenburgB.B. MateK.K.V. McAlindenC. McGrathJ.J. MehtaV. MeierT. MelesH.G. MeleseA. MemiahP.T.N. MemishZ.A. MendozaW. MengistuD.T. MengistuG. MeretojaA. MeretojaT.J. MestrovicT. MiazgowskiB. MiazgowskiT. MillerT.R. MiniG.K. MirrakhimovE.M. MoazenB. MohajerB. Mohammad Gholi MezerjiN. MohammadiM. Mohammadi-KhanaposhtaniM. MohammadibakhshR. Mohammadnia-AfrouziM. MohammedS. MohebiF. MokdadA.H. MonastaL. MondelloS. MoodleyY. MoosazadehM. MoradiG. Moradi-LakehM. MoradinazarM. MoragaP. Moreno VelásquezI. MorrisonS.D. MousaviS.M. MuhammedO.S. MuruetW. MusaK.I. MustafaG. NaderiM. NagelG. NaheedA. NaikG. NajafiF. NangiaV. NegoiI. NegoiR.I. NewtonC.R.J. NgunjiriJ.W. NguyenC.T. NguyenL.H. NingrumD.N.A. NirayoY.L. NixonM.R. NorrvingB. NoubiapJ.J. Nourollahpour ShiadehM. NyasuluP.S. OgahO.S. OhI-H. OlagunjuA.T. OlagunjuT.O. OlivaresP.R. OnwujekweO.E. OrenE. OwolabiM.O. PaM. PakpourA.H. PanW-H. Panda-JonasS. PandianJ.D. PatelS.K. PereiraD.M. PetzoldM. PillayJ.D. PiradovM.A. PolanczykG.V. PolinderS. PostmaM.J. PoultonR. PoustchiH. PrakashS. PrakashV. QorbaniM. RadfarA. RafayA. RafieiA. RahimF. Rahimi-MovagharV. RahmanM. RahmanM.H.U. RahmanM.A. RajatiF. RamU. RantaA. RawafD.L. RawafS. ReinigN. ReisC. RenzahoA.M.N. ResnikoffS. RezaeianS. RezaiM.S. Rios GonzálezC.M. RobertsN.L.S. RoeverL. RonfaniL. RoroE.M. RoshandelG. RostamiA. SabbaghP. SaccoR.L. SachdevP.S. SaddikB. SafariH. Safari-FaramaniR. SafiS. SafiriS. SagarR. SahathevanR. SahebkarA. SahraianM.A. SalamatiP. Salehi ZahabiS. SalimiY. SamyA.M. SanabriaJ. SantosI.S. Santric MilicevicM.M. SarrafzadeganN. SartoriusB. SarviS. SathianB. SatpathyM. SawantA.R. SawhneyM. SchneiderI.J.C. SchöttkerB. SchwebelD.C. SeedatS. SepanlouS.G. ShabaninejadH. ShafieesabetA. ShaikhM.A. ShakirR.A. Shams-BeyranvandM. ShamsizadehM. SharifM. Sharif-AlhoseiniM. SheJ. SheikhA. ShethK.N. ShigematsuM. ShiriR. ShirkoohiR. ShiueI. SiabaniS. SiddiqiT.J. SigfusdottirI.D. SigurvinsdottirR. SilberbergD.H. SilvaJ.P. SilveiraD.G.A. SinghJ.A. SinhaD.N. SkiadaresiE. SmithM. SobaihB.H. SobhaniS. SoofiM. SoyiriI.N. SposatoL.A. SteinD.J. SteinM.B. StokesM.A. SufiyanM.B. SykesB.L. SylajaP.N. Tabarés-SeisdedosR. Te AoB.J. Tehrani-BanihashemiA. TemsahM-H. TemsahO. ThakurJ.S. ThriftA.G. Topor-MadryR. Tortajada-GirbésM. Tovani-PaloneM.R. TranB.X. TranK.B. TruelsenT.C. TsadikA.G. Tudor CarL. UkwajaK.N. UllahI. UsmanM.S. UthmanO.A. ValdezP.R. VasankariT.J. VasanthanR. VeisaniY. VenketasubramanianN. ViolanteF.S. VlassovV. VosoughiK. VuG.T. VujcicI.S. WagnewF.S. WaheedY. WangY-P. WeiderpassE. WeissJ. WhitefordH.A. WijeratneT. WinklerA.S. WiysongeC.S. WolfeC.D.A. XuG. YadollahpourA. YamadaT. YanoY. YaseriM. YatsuyaH. YimerE.M. YipP. YismaE. YonemotoN. YousefifardM. YuC. ZaidiZ. ZamanS.B. ZamaniM. ZandianH. ZareZ. ZhangY. ZodpeyS. NaghaviM. MurrayC.J.L. VosT. GBD 2016 Neurology Collaborators Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet Neurol.201918545948010.1016/S1474‑4422(18)30499‑X30879893
     [Google Scholar]
  4. BrookmeyerR. JohnsonE. Ziegler-GrahamK. ArrighiH.M. Forecasting the global burden of Alzheimer’s disease.Alzheimers Dement.20073318619110.1016/j.jalz.2007.04.38119595937
     [Google Scholar]
  5. CornutiuG. The epidemiological scale of Alzheimer’s disease.J. Clin. Med. Res.20157965766610.14740/jocmr2106w26251678
     [Google Scholar]
  6. BattogtokhG. ChoiY.S. KangD.S. ParkS.J. ShimM.S. HuhK.M. ChoY.Y. LeeJ.Y. LeeH.S. KangH.C. Mitochondria-targeting drug conjugates for cytotoxic, anti-oxidizing and sensing purposes: current strategies and future perspectives.Acta Pharm. Sin. B20188686288010.1016/j.apsb.2018.05.00630505656
     [Google Scholar]
  7. OnyangoI.G. DennisJ. KhanS.M. Mitochondrial dysfunction in Alzheimer’s disease and the rationale for bioenergetics based therapies.Aging Dis.20167220121410.14336/AD.2015.100727114851
     [Google Scholar]
  8. TangJ. OliverosA. JangM.H. Dysfunctional mitochondrial bioenergetics and synaptic degeneration in Alzheimer disease.Int. Neurourol. J.201923Suppl. 1S5S1010.5213/inj.1938036.01830832462
     [Google Scholar]
  9. ZhangX. ZhaoD. WuW. Ali ShahS.Z. LaiM. YangD. LiJ. GuanZ. LiW. GaoH. ZhaoH. ZhouX. YangL. Melatonin regulates mitochondrial dynamics and alleviates neuron damage in prion diseases.Aging (Albany NY)20201211111391115110.18632/aging.10332832526704
     [Google Scholar]
  10. SavelieffM.G. NamG. KangJ. LeeH.J. LeeM. LimM.H. Development of multifunctional molecules as potential therapeutic candidates for Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis in the last decade.Chem. Rev.201911921221132210.1021/acs.chemrev.8b0013830095897
     [Google Scholar]
  11. SulimanH.B. PiantadosiC.A. Mitochondrial quality control as a therapeutic target.Pharmacol. Rev.2016681204810.1124/pr.115.01150226589414
     [Google Scholar]
  12. EckertG.P. RennerK. EckertS.H. EckmannJ. HaglS. Abdel-KaderR.M. KurzC. LeunerK. MullerW.E. Mitochondrial dysfunction--a pharmacological target in Alzheimer’s disease.Mol. Neurobiol.201246113615010.1007/s12035‑012‑8271‑z22552779
     [Google Scholar]
  13. FarlowM.R. MillerM.L. PejovicV. Treatment options in Alzheimer’s disease: maximizing benefit, managing expectations.Dement. Geriatr. Cogn. Disord.200825540842210.1159/00012296218391487
     [Google Scholar]
  14. CasleyC.S. CanevariL. LandJ.M. ClarkJ.B. SharpeM.A. β-Amyloid inhibits integrated mitochondrial respiration and key enzyme activities.J. Neurochem.20028019110010.1046/j.0022‑3042.2001.00681.x11796747
     [Google Scholar]
  15. ZhaoY. ZhaoB. Oxidative stress and the pathogenesis of Alzheimer's disease.Oxidative med. cell. longev.2013201331652310.1155/2013/316523
     [Google Scholar]
  16. PaganiL. EckertA. Amyloid-Beta interaction with mitochondria.Int. J. Alzheimer’s Dis.2011201192505010.4061/2011/925050
     [Google Scholar]
  17. JohriA. BealM.F. Mitochondrial dysfunction in neurodegenerative diseases.J. Pharmacol. Exp. Ther.2012342361963010.1124/jpet.112.19213822700435
     [Google Scholar]
  18. IshiharaN. EuraY. MiharaK. Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity.J. Cell Sci.2004117266535654610.1242/jcs.0156515572413
     [Google Scholar]
  19. FrezzaC. CipolatS. Martins de BritoO. MicaroniM. BeznoussenkoG.V. RudkaT. BartoliD. PolishuckR.S. DanialN.N. De StrooperB. ScorranoL. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion.Cell2006126117718910.1016/j.cell.2006.06.02516839885
     [Google Scholar]
  20. TakahataM. TamuraT. AbeK. MiharaH. KurokawaS. YamamotoY. NakanoR. EsakiN. InagakiK. Selenite assimilation into formate dehydrogenase H depends on thioredoxin reductase in Escherichia coli.J. Biochem.2007143446747310.1093/jb/mvm24718182386
     [Google Scholar]
  21. ChenH. DetmerS.A. EwaldA.J. GriffinE.E. FraserS.E. ChanD.C. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development.J. Cell Biol.2003160218920010.1083/jcb.20021104612527753
     [Google Scholar]
  22. SongZ. ChenH. FiketM. AlexanderC. ChanD.C. OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L.J. Cell Biol.2007178574975510.1083/jcb.20070411017709429
     [Google Scholar]
  23. SatohM. HamamotoT. SeoN. KagawaY. EndoH. Differential sublocalization of the dynamin-related protein OPA1 isoforms in mitochondria.Biochem. Biophys. Res. Commun.2003300248249310.1016/S0006‑291X(02)02874‑712504110
     [Google Scholar]
  24. CipolatS. RudkaT. HartmannD. CostaV. SerneelsL. CraessaertsK. MetzgerK. FrezzaC. AnnaertW. D’AdamioL. DerksC. DejaegereT. PellegriniL. D’HoogeR. ScorranoL. De StrooperB. Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling.Cell2006126116317510.1016/j.cell.2006.06.02116839884
     [Google Scholar]
  25. ConsolatoF. MalteccaF. TulliS. SambriI. CasariG. m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics.J. Cell Sci.20181317jcs21354610.1242/jcs.21354629545505
     [Google Scholar]
  26. XuD.P. LiY. MengX. ZhouT. ZhouY. ZhengJ. ZhangJ.J. LiH.B. Natural antioxidants in foods and medicinal plants: Extraction, assessment and resources.Int. J. Mol. Sci.20171819610.3390/ijms1801009628067795
     [Google Scholar]
  27. KarbowskiM. JeongS.Y. YouleR.J. Endophilin B1 is required for the maintenance of mitochondrial morphology.J. Cell Biol.200416671027103910.1083/jcb.20040704615452144
     [Google Scholar]
  28. SteffenJ. KoehlerC.M. ER–mitochondria contacts: Actin dynamics at the ER control mitochondrial fission via calcium release.J. Cell Biol.20182171151710.1083/jcb.20171107529259094
     [Google Scholar]
  29. AnandR. WaiT. BakerM.J. KladtN. SchaussA.C. RugarliE. LangerT. The i -AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission.J. Cell Biol.2014204691992910.1083/jcb.20130800624616225
     [Google Scholar]
  30. CaiN. WuY. HuangY. Induction of accelerated aging in a mouse model.Cells2022119141810.3390/cells1109141835563724
     [Google Scholar]
  31. ManczakM. ReddyP.H. Abnormal interaction between the mitochondrial fission protein Drp1 and hyperphosphorylated tau in Alzheimer’s disease neurons: implications for mitochondrial dysfunction and neuronal damage.Hum. Mol. Genet.201221112538254710.1093/hmg/dds07222367970
     [Google Scholar]
  32. GrimmA. LimY.A. Mensah-NyaganA.G. GötzJ. EckertA. Alzheimer’s disease, oestrogen and mitochondria: an ambiguous relationship.Mol. Neurobiol.201246115116010.1007/s12035‑012‑8281‑x22678467
     [Google Scholar]
  33. SarkarS. JunS. SimpkinsJ.W. Estrogen amelioration of Aβ-induced defects in mitochondria is mediated by mitochondrial signaling pathway involving ERβ, AKAP and Drp1.Brain Res.2015161610111110.1016/j.brainres.2015.04.05925964165
     [Google Scholar]
  34. NakamuraT. CieplakP. ChoD.H. GodzikA. LiptonS.A. S-Nitrosylation of Drp1 links excessive mitochondrial fission to neuronal injury in neurodegeneration.Mitochondrion201010557357810.1016/j.mito.2010.04.00720447471
     [Google Scholar]
  35. FlanneryP.J. TrushinaE. Mitochondrial dynamics and transport in Alzheimer’s disease.Mol. Cell. Neurosci.20199810912010.1016/j.mcn.2019.06.00931216425
     [Google Scholar]
  36. HollenbeckP.J. SaxtonW.M. The axonal transport of mitochondria.J. Cell Sci.2005118235411541910.1242/jcs.0274516306220
     [Google Scholar]
  37. LinM.Y. ShengZ.H. Regulation of mitochondrial transport in neurons.Exp. Cell Res.20153341354410.1016/j.yexcr.2015.01.00425612908
     [Google Scholar]
  38. NambaT. FunahashiY. NakamutaS. XuC. TakanoT. KaibuchiK. Extracellular and intracellular signaling for neuronal polarity.Physiol. Rev.2015953995102410.1152/physrev.00025.201426133936
     [Google Scholar]
  39. TrushinaE. NemutluE. ZhangS. ChristensenT. CampJ. MesaJ. SiddiquiA. TamuraY. SesakiH. WengenackT.M. DzejaP.P. PodusloJ.F. Defects in mitochondrial dynamics and metabolomic signatures of evolving energetic stress in mouse models of familial Alzheimer’s disease.PLoS One201272e3273710.1371/journal.pone.003273722393443
     [Google Scholar]
  40. CalkinsM.J. ManczakM. MaoP. ShirendebU. ReddyP.H. Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer’s disease.Hum. Mol. Genet.201120234515452910.1093/hmg/ddr38121873260
     [Google Scholar]
  41. CaiQ. TammineniP. Mitochondrial aspects of synaptic dysfunction in Alzheimer’s disease.J. Alzheimers Dis.20175741087110310.3233/JAD‑16072627767992
     [Google Scholar]
  42. CourseM.M. WangX. Transporting mitochondria in neurons.F1000 Res.20165173510.12688/f1000research.7864.127508065
     [Google Scholar]
  43. PathakD. SeppK.J. HollenbeckP.J. Evidence that myosin activity opposes microtubule-based axonal transport of mitochondria.J. Neurosci.201030268984899210.1523/JNEUROSCI.1621‑10.201020592219
     [Google Scholar]
  44. ShneyerB.I. UšajM. HennA. Myo19 is an outer mitochondrial membrane motor and effector of starvation-induced filopodia.J. Cell Sci.2016129354355610.1242/jcs.17534926659663
     [Google Scholar]
  45. QuinteroO.A. DiVitoM.M. AdikesR.C. KortanM.B. CaseL.B. LierA.J. PanaretosN.S. SlaterS.Q. RengarajanM. FeliuM. CheneyR.E. Human Myo19 is a novel myosin that associates with mitochondria.Curr. Biol.200919232008201310.1016/j.cub.2009.10.02619932026
     [Google Scholar]
  46. MiskoA. JiangS. WegorzewskaI. MilbrandtJ. BalohR.H. Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex.J. Neurosci.201030124232424010.1523/JNEUROSCI.6248‑09.201020335458
     [Google Scholar]
  47. MaH. CaiQ. LuW. ShengZ.H. MochidaS. KIF5B motor adaptor syntabulin maintains synaptic transmission in sympathetic neurons.J. Neurosci.20092941130191302910.1523/JNEUROSCI.2517‑09.200919828815
     [Google Scholar]
  48. MacAskillA.F. KittlerJ.T. Control of mitochondrial transport and localization in neurons.Trends Cell Biol.201020210211210.1016/j.tcb.2009.11.00220006503
     [Google Scholar]
  49. PekkurnazG. TrinidadJ.C. WangX. KongD. SchwarzT.L. Glucose regulates mitochondrial motility via Milton modification by O-GlcNAc transferase.Cell20141581546810.1016/j.cell.2014.06.00724995978
     [Google Scholar]
  50. LiY. LimS. HoffmanD. AspenstromP. FederoffH.J. RempeD.A. HUMMR, a hypoxia- and HIF-1α–inducible protein, alters mitochondrial distribution and transport.J. Cell Biol.200918561065108110.1083/jcb.20081103319528298
     [Google Scholar]
  51. MironovS.L. ADP regulates movements of mitochondria in neurons.Biophys. J.20079282944295210.1529/biophysj.106.09298117277190
     [Google Scholar]
  52. Reck-PetersonS.L. RedwineW.B. ValeR.D. CarterA.P. The cytoplasmic dynein transport machinery and its many cargoes.Nat. Rev. Mol. Cell Biol.201819638239810.1038/s41580‑018‑0004‑329662141
     [Google Scholar]
  53. López-DoménechG. Covill-CookeC. IvankovicD. HalffE.F. SheehanD.F. NorkettR. BirsaN. KittlerJ.T. Miro proteins coordinate microtubule- and actin-dependent mitochondrial transport and distribution.EMBO J.201837332133610.15252/embj.20169638029311115
     [Google Scholar]
  54. MelkovA. AbduU. Regulation of long-distance transport of mitochondria along microtubules.Cell. Mol. Life Sci.201875216317610.1007/s00018‑017‑2590‑128702760
     [Google Scholar]
  55. YouleR.J. van der BliekA.M. Mitochondrial fission, fusion, and stress.Science201233760981062106510.1126/science.121985522936770
     [Google Scholar]
  56. StokinG.B. LilloC. FalzoneT.L. BruschR.G. RockensteinE. MountS.L. RamanR. DaviesP. MasliahE. WilliamsD.S. GoldsteinL.S.B. Axonopathy and transport deficits early in the pathogenesis of Alzheimer’s disease.Science200530757131282128810.1126/science.110568115731448
     [Google Scholar]
  57. WangX. PerryG. SmithM.A. ZhuX. Amyloid-β-derived diffusible ligands cause impaired axonal transport of mitochondria in neurons.Neurodegener. Dis.201071-3565910.1159/00028348420160460
     [Google Scholar]
  58. DuH. GuoL. YanS. SosunovA.A. McKhannG.M. ShiDu YanS. Early deficits in synaptic mitochondria in an Alzheimer’s disease mouse model.Proc. Natl. Acad. Sci. USA201010743186701867510.1073/pnas.100658610720937894
     [Google Scholar]
  59. VosselK.A. ZhangK. BrodbeckJ. DaubA.C. SharmaP. FinkbeinerS. CuiB. MuckeL. Tau reduction prevents Abeta-induced defects in axonal transport.Science2010330600119819810.1126/science.119465320829454
     [Google Scholar]
  60. ZhangL. TrushinS. ChristensenT.A. TripathiU. HongC. GerouxR.E. HowellK.G. PodusloJ.F. TrushinaE. Differential effect of amyloid beta peptides on mitochondrial axonal trafficking depends on their state of aggregation and binding to the plasma membrane.Neurobiol. Dis.201811411610.1016/j.nbd.2018.02.00329477640
     [Google Scholar]
  61. ChengY. BaiF. The association of tau with mitochondrial dysfunction in Alzheimer’s disease.Front. Neurosci.20181216310.3389/fnins.2018.0016329623026
     [Google Scholar]
  62. KimI. LemastersJ.J. Mitochondrial degradation by autophagy (mitophagy) in GFP-LC3 transgenic hepatocytes during nutrient deprivation.Am. J. Physiol. Cell Physiol.20113002C308C31710.1152/ajpcell.00056.201021106691
     [Google Scholar]
  63. LemastersJ.J. Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging.Rejuvenation Res.2005813510.1089/rej.2005.8.315798367
     [Google Scholar]
  64. BolisettyS. JaimesE. Mitochondria and reactive oxygen species: physiology and pathophysiology.Int. J. Mol. Sci.20131436306634410.3390/ijms1403630623528859
     [Google Scholar]
  65. TaylorR. GoldmanS.J. Mitophagy and disease: new avenues for pharmacological intervention.Curr. Pharm. Des.201117202056207310.2174/13816121179690476821718245
     [Google Scholar]
  66. KimI. Rodriguez-EnriquezS. LemastersJ.J. Selective degradation of mitochondria by mitophagy.Arch. Biochem. Biophys.2007462224525310.1016/j.abb.2007.03.03417475204
     [Google Scholar]
  67. GuoC. SunL. ChenX. ZhangD. Oxidative stress, mitochondrial damage and neurodegenerative diseases.Neural Regen. Res.20138212003201425206509
     [Google Scholar]
  68. ZorovD.B. JuhaszovaM. SollottS.J. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release.Physiol. Rev.201494390995010.1152/physrev.00026.201324987008
     [Google Scholar]
  69. CalabreseV. CorneliusC. StellaA.M.G. CalabreseE.J. Cellular stress responses, mitostress and carnitine insufficiencies as critical determinants in aging and neurodegenerative disorders: role of hormesis and vitagenes.Neurochem. Res.201035121880191510.1007/s11064‑010‑0307‑z21080068
     [Google Scholar]
  70. GhavamiS. ShojaeiS. YeganehB. AndeS.R. JangamreddyJ.R. MehrpourM. ChristofferssonJ. ChaabaneW. MoghadamA.R. KashaniH.H. HashemiM. OwjiA.A. ŁosM.J. Autophagy and apoptosis dysfunction in neurodegenerative disorders.Prog. Neurobiol.2014112244910.1016/j.pneurobio.2013.10.00424211851
     [Google Scholar]
  71. ZhangT. XueL. LiL. TangC. WanZ. WangR. TanJ. TanY. HanH. TianR. BilliarT.R. TaoW.A. ZhangZ. BNIP3 protein suppresses PINK1 kinase proteolytic cleavage to promote mitophagy.J. Biol. Chem.201629141216162162910.1074/jbc.M116.73341027528605
     [Google Scholar]
  72. VincowE.S. MerrihewG. ThomasR.E. ShulmanN.J. BeyerR.P. MacCossM.J. PallanckL.J. The PINK1–Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo.Proc. Natl. Acad. Sci. USA2013110166400640510.1073/pnas.122113211023509287
     [Google Scholar]
  73. SekineS. KanamaruY. KoikeM. NishiharaA. OkadaM. KinoshitaH. KamiyamaM. MaruyamaJ. UchiyamaY. IshiharaN. TakedaK. IchijoH. Rhomboid protease PARL mediates the mitochondrial membrane potential loss-induced cleavage of PGAM5.J. Biol. Chem.201228741346353464510.1074/jbc.M112.35750922915595
     [Google Scholar]
  74. ScarffeL.A. StevensD.A. DawsonV.L. DawsonT.M. Parkin and PINK1: much more than mitophagy.Trends Neurosci.201437631532410.1016/j.tins.2014.03.00424735649
     [Google Scholar]
  75. HeoJ.M. OrdureauA. PauloJ.A. RinehartJ. HarperJ.W. The PINK1-PARKIN mitochondrial ubiquitylation pathway drives a program of OPTN/NDP52 recruitment and TBK1 activation to promote mitophagy.Mol. Cell201560172010.1016/j.molcel.2015.08.01626365381
     [Google Scholar]
  76. AshrafiG. SchwarzT.L. The pathways of mitophagy for quality control and clearance of mitochondria.Cell Death Differ.2013201314210.1038/cdd.2012.8122743996
     [Google Scholar]
  77. KangR. ZehH.J. LotzeM.T. TangD. The Beclin 1 network regulates autophagy and apoptosis.Cell Death Differ.201118457158010.1038/cdd.2010.19121311563
     [Google Scholar]
  78. TammineniP. Impaired retrograde transport of axonal autophagosomes contributes to autophagic stress in Alzheimer’s disease neurons.elife20176e2177610.7554/eLife.21776
     [Google Scholar]
  79. NixonR.A. WegielJ. KumarA. YuW.H. PeterhoffC. CataldoA. CuervoA.M. Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study.J. Neuropathol. Exp. Neurol.200564211312210.1093/jnen/64.2.11315751225
     [Google Scholar]
  80. NixonR.A. Autophagy, amyloidogenesis and Alzheimer disease.J. Cell Sci.2007120234081409110.1242/jcs.01926518032783
     [Google Scholar]
  81. HällbergB.M. LarssonN.G. Making proteins in the powerhouse.Cell Metab.201420222624010.1016/j.cmet.2014.07.00125088301
     [Google Scholar]
  82. Ventura-ClapierR. GarnierA. VekslerV. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1.Cardiovasc. Res.200879220821710.1093/cvr/cvn09818430751
     [Google Scholar]
  83. ChoiH.I. KimH.J. ParkJ.S. KimI.J. BaeE.H. MaS.K. KimS.W. PGC-1α attenuates hydrogen peroxide-induced apoptotic cell death by upregulating Nrf-2 via GSK3β inactivation mediated by activated p38 in HK-2 Cells.Sci. Rep.201771431910.1038/s41598‑017‑04593‑w28659586
     [Google Scholar]
  84. QinW. HaroutunianV. KatselP. CardozoC.P. HoL. BuxbaumJ.D. PasinettiG.M. PGC-1α expression decreases in the Alzheimer disease brain as a function of dementia.Arch. Neurol.200966335236110.1001/archneurol.2008.58819273754
     [Google Scholar]
  85. RiceA.C. KeeneyP.M. AlgarzaeN.K. LaddA.C. ThomasR.R. BennettJ.P.Jr Mitochondrial DNA copy numbers in pyramidal neurons are decreased and mitochondrial biogenesis transcriptome signaling is disrupted in Alzheimer’s disease hippocampi.J. Alzheimers Dis.201440231933010.3233/JAD‑13171524448779
     [Google Scholar]
  86. SajanM. HansenB. IveyR.III SajanJ. AriC. SongS. BraunU. LeitgesM. Farese-HiggsM. FareseR.V. Brain insulin signaling is increased in insulin-resistant states and decreases in FOXOs and PGC-1α and increases in Aβ1–40/42 and phospho-tau may abet Alzheimer development.Diabetes20166571892190310.2337/db15‑142826895791
     [Google Scholar]
  87. ShengB. WangX. SuB. LeeH. CasadesusG. PerryG. ZhuX. Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer’s disease.J. Neurochem.2012120341942910.1111/j.1471‑4159.2011.07581.x22077634
     [Google Scholar]
  88. RobinsonA. GrösgenS. MettJ. ZimmerV.C. HaupenthalV.J. HundsdörferB. StahlmannC.P. SlobodskoyY. MüllerU.C. HartmannT. SteinR. GrimmM.O. Upregulation of PGC-1α expression by Alzheimer’s disease-associated pathway: presenilin 1/amyloid precursor protein (APP)/intracellular domain of APP.Aging Cell201413226327210.1111/acel.1218324304563
     [Google Scholar]
  89. KatsouriL. ParrC. BogdanovicN. WillemM. SastreM. PPARγ co-activator-1α (PGC-1α) reduces amyloid-β generation through a PPARγ-dependent mechanism.J. Alzheimers Dis.201125115116210.3233/JAD‑2011‑10135621358044
     [Google Scholar]
  90. WangR. LiJ.J. DiaoS. KwakY.D. LiuL. ZhiL. BüelerH. BhatN.R. WilliamsR.W. ParkE.A. LiaoF.F. Metabolic stress modulates Alzheimer’s β-secretase gene transcription via SIRT1-PPARγ-PGC-1 in neurons.Cell Metab.201317568569410.1016/j.cmet.2013.03.01623663737
     [Google Scholar]
  91. KatsouriL. LimY.M. BlondrathK. EleftheriadouI. LombarderoL. BirchA.M. MirzaeiN. IrvineE.E. MazarakisN.D. SastreM. PPARγ-coactivator-1α gene transfer reduces neuronal loss and amyloid-β generation by reducing β-secretase in an Alzheimer’s disease model.Proc. Natl. Acad. Sci. USA201611343122921229710.1073/pnas.160617111327791018
     [Google Scholar]
  92. DumontM. StackC. ElipenahliC. JainuddinS. LaunayN. GergesM. StarkovaN. StarkovA.A. CalingasanN.Y. TampelliniD. PujolA. BealM.F. PGC-1α: overexpression exacerbates β-amyloid and tau deposition in a transgenic mouse model of Alzheimer’s disease.FASEB J.20142841745175510.1096/fj.13‑23633124398293
     [Google Scholar]
  93. RussellL.K. MansfieldC.M. LehmanJ.J. KovacsA. CourtoisM. SaffitzJ.E. MedeirosD.M. ValencikM.L. McDonaldJ.A. KellyD.P. Cardiac-specific induction of the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1α promotes mitochondrial biogenesis and reversible cardiomyopathy in a developmental stage-dependent manner.Circ. Res.200494452553310.1161/01.RES.0000117088.36577.EB14726475
     [Google Scholar]
  94. BalabanR.S. NemotoS. FinkelT. Mitochondria, oxidants, and aging.cell2005120448349510.1016/j.cell.2005.02.001
     [Google Scholar]
  95. ButterfieldD.A. HalliwellB. Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease.Nat. Rev. Neurosci.201920314816010.1038/s41583‑019‑0132‑630737462
     [Google Scholar]
  96. WangX. WangW. LiL. PerryG. LeeH. ZhuX. Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease.Biochim. Biophys. Acta Mol. Basis Dis.2014184281240124710.1016/j.bbadis.2013.10.01524189435
     [Google Scholar]
  97. ZhuX. CastellaniR.J. MoreiraP.I. AlievG. ShenkJ.C. SiedlakS.L. HarrisP.L.R. FujiokaH. SayreL.M. SzwedaP.A. SzwedaL.I. SmithM.A. PerryG. Hydroxynonenal-generated crosslinking fluorophore accumulation in Alzheimer disease reveals a dichotomy of protein turnover.Free Radic. Biol. Med.201252369970410.1016/j.freeradbiomed.2011.11.00422137893
     [Google Scholar]
  98. NunomuraA. TamaokiT. MotohashiN. NakamuraM. McKeelD.W.Jr TabatonM. LeeH. SmithM.A. PerryG. ZhuX. The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons.J. Neuropathol. Exp. Neurol.201271323324110.1097/NEN.0b013e318248e61422318126
     [Google Scholar]
  99. MandalP.K. SaharanS. TripathiM. MurariG. Brain glutathione levels--a novel biomarker for mild cognitive impairment and Alzheimer’s disease.Biol. Psychiatry2015781070271010.1016/j.biopsych.2015.04.00526003861
     [Google Scholar]
  100. ShuklaD. MandalP.K. TripathiM. VishwakarmaG. MishraR. SandalK. Quantitation of in vivo brain glutathione conformers in cingulate cortex among age-matched control, MCI, and AD patients using MEGA-PRESS.Hum. Brain Mapp.202041119421710.1002/hbm.2479931584232
     [Google Scholar]
  101. ScheffS.W. AnsariM.A. MufsonE.J. Oxidative stress and hippocampal synaptic protein levels in elderly cognitively intact individuals with Alzheimer’s disease pathology.Neurobiol. Aging20164211210.1016/j.neurobiolaging.2016.02.03027143416
     [Google Scholar]
  102. BaekS.H. ParkS.J. JeongJ.I. KimS.H. HanJ. KyungJ.W. BaikS.H. ChoiY. ChoiB.Y. ParkJ.S. BahnG. ShinJ.H. JoD.S. LeeJ.Y. JangC.G. ArumugamT.V. KimJ. HanJ.W. KohJ.Y. ChoD.H. JoD.G. Inhibition of Drp1 ameliorates synaptic depression, Aβ deposition, and cognitive impairment in an Alzheimer’s disease model.J. Neurosci.201737205099511010.1523/JNEUROSCI.2385‑16.201728432138
     [Google Scholar]
  103. EstaquierJ. ArnoultD. Inhibiting Drp1-mediated mitochondrial fission selectively prevents the release of cytochrome c during apoptosis.Cell Death Differ.20071461086109410.1038/sj.cdd.440210717332775
     [Google Scholar]
  104. ManczakM. ReddyP.H. Mitochondrial division inhibitor 1 protects against mutant huntingtin-induced abnormal mitochondrial dynamics and neuronal damage in Huntington’s disease.Hum. Mol. Genet.201524257308732510.1093/hmg/ddv42926464486
     [Google Scholar]
  105. ReddyP.H. ManczakM. YinX. GradyM.C. MitchellA. TonkS. KuruvaC.S. BhattiJ.S. KandimallaR. VijayanM. KumarS. WangR. PradeepkiranJ.A. OgunmokunG. ThamaraiK. QuesadaK. BolesA. ReddyA.P. Protective effects of Indian spice curcumin against amyloid-β in Alzheimer’s disease.J. Alzheimers Dis.201861384386610.3233/JAD‑17051229332042
     [Google Scholar]
  106. ReddyP.H. OliverD.M.A. Amyloid beta and phosphorylated tau-induced defective autophagy and mitophagy in Alzheimer’s disease.Cells20198548810.3390/cells805048831121890
     [Google Scholar]
  107. MedalaV.K. GollapelliB. DewanjeeS. OgunmokunG. KandimallaR. VallamkonduJ. Mitochondrial dysfunction, mitophagy, and role of dynamin-related protein 1 in Alzheimer’s disease.J. Neurosci. Res.20219941120113510.1002/jnr.2478133465841
     [Google Scholar]
  108. RosdahA.A. K HolienJ. DelbridgeL.M. DustingG.J. LimS.Y. Mitochondrial fission - a drug target for cytoprotection or cytodestruction?Pharmacol. Res. Perspect.201643e0023510.1002/prp2.23527433345
     [Google Scholar]
  109. MaciaE. EhrlichM. MassolR. BoucrotE. BrunnerC. KirchhausenT. Dynasore, a cell-permeable inhibitor of dynamin.Dev. Cell200610683985010.1016/j.devcel.2006.04.00216740485
     [Google Scholar]
  110. KuruvaC.S. ManczakM. YinX. OgunmokunG. ReddyA.P. ReddyP.H. Aqua-soluble DDQ reduces the levels of Drp1 and Aβ and inhibits abnormal interactions between Aβ and Drp1 and protects Alzheimer’s disease neurons from Aβ- and Drp1-induced mitochondrial and synaptic toxicities.Hum. Mol. Genet.201726173375339510.1093/hmg/ddx22628854701
     [Google Scholar]
  111. FilichiaE. HofferB. QiX. LuoY. Inhibition of Drp1 mitochondrial translocation provides neural protection in dopaminergic system in a Parkinson’s disease model induced by MPTP.Sci. Rep.2016613265610.1038/srep3265627619562
     [Google Scholar]
  112. FerreiraJ.C.B. CamposJ.C. QvitN. QiX. BoziL.H.M. BecharaL.R.G. LimaV.M. QueliconiB.B. DisatnikM.H. DouradoP.M.M. KowaltowskiA.J. Mochly-RosenD. A selective inhibitor of mitofusin 1-βIIPKC association improves heart failure outcome in rats.Nat. Commun.201910132910.1038/s41467‑018‑08276‑630659190
     [Google Scholar]
  113. SzaboA. SumegiK. FeketeK. HocsakE. DebreceniB. SetaloG.Jr KovacsK. DeresL. KengyelA. KovacsD. MandlJ. NyitraiM. FebbraioM.A. GallyasF.Jr SumegiB. Activation of mitochondrial fusion provides a new treatment for mitochondria-related diseases.Biochem. Pharmacol.2018150869610.1016/j.bcp.2018.01.03829378182
     [Google Scholar]
  114. Miret-CasalsL. Identification of new activators of mitochondrial fusion reveals a link between mitochondrial morphology and pyrimidine metabolism.Cell chemical biol.201825326827810.1016/j.chembiol.2017.12.001
     [Google Scholar]
  115. WangD. WangJ. BonamyG.M.C. MeeusenS. BruschR.G. TurkC. YangP. SchultzP.G. A small molecule promotes mitochondrial fusion in mammalian cells.Angew. Chem. Int. Ed.201251379302930510.1002/anie.20120458922907892
     [Google Scholar]
  116. PengK. YangL. WangJ. YeF. DanG. ZhaoY. CaiY. CuiZ. AoL. LiuJ. ZouZ. SaiY. CaoJ. The interaction of mitochondrial biogenesis and fission/fusion mediated by PGC-1α regulates rotenone-induced dopaminergic neurotoxicity.Mol. Neurobiol.20175453783379710.1007/s12035‑016‑9944‑927271125
     [Google Scholar]
  117. RaefskyS.M. MattsonM.P. Adaptive responses of neuronal mitochondria to bioenergetic challenges: Roles in neuroplasticity and disease resistance.Free Radic. Biol. Med.201710220321610.1016/j.freeradbiomed.2016.11.04527908782
     [Google Scholar]
  118. AlirezaeiM. KemballC.C. FlynnC.T. WoodM.R. WhittonJ.L. KiossesW.B. Short-term fasting induces profound neuronal autophagy.Autophagy20106670271010.4161/auto.6.6.1237620534972
     [Google Scholar]
  119. ChengA. YangY. ZhouY. MaharanaC. LuD. PengW. LiuY. WanR. MarosiK. MisiakM. BohrV.A. MattsonM.P. Mitochondrial SIRT3 mediates adaptive responses of neurons to exercise and metabolic and excitatory challenges.Cell Metab.201623112814210.1016/j.cmet.2015.10.01326698917
     [Google Scholar]
  120. KerrJ.S. AdriaanseB.A. GreigN.H. MattsonM.P. CaderM.Z. BohrV.A. FangE.F. Mitophagy and Alzheimer’s disease: cellular and molecular mechanisms.Trends Neurosci.201740315116610.1016/j.tins.2017.01.00228190529
     [Google Scholar]
  121. WangX. SuB. LeeH. LiX. PerryG. SmithM.A. ZhuX. Impaired balance of mitochondrial fission and fusion in Alzheimer’s disease.J. Neurosci.200929289090910310.1523/JNEUROSCI.1357‑09.200919605646
     [Google Scholar]
  122. RodgerC.E. McWilliamsT.G. GanleyI.G. Mammalian mitophagy – from in vitro molecules to in vivo models.FEBS J.201828571185120210.1111/febs.1433629151277
     [Google Scholar]
  123. KangC. Li JiL. Role of PGC-1α signaling in skeletal muscle health and disease.Ann. N. Y. Acad. Sci.20121271111011710.1111/j.1749‑6632.2012.06738.x23050972
     [Google Scholar]
  124. ChengA. WanR. YangJ.L. KamimuraN. SonT.G. OuyangX. LuoY. OkunE. MattsonM.P. Involvement of PGC-1α in the formation and maintenance of neuronal dendritic spines.Nat. Commun.201231125010.1038/ncomms223823212379
     [Google Scholar]
  125. RyuD. MouchiroudL. AndreuxP.A. KatsyubaE. MoullanN. Nicolet-dit-FélixA.A. WilliamsE.G. JhaP. Lo SassoG. HuzardD. AebischerP. SandiC. RinschC. AuwerxJ. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents.Nat. Med.201622887988810.1038/nm.413227400265
     [Google Scholar]
  126. RichterU. LahtinenT. MarttinenP. SuomiF. BattersbyB.J. Quality control of mitochondrial protein synthesis is required for membrane integrity and cell fitness.J. Cell Biol.2015211237338910.1083/jcb.20150406226504172
     [Google Scholar]
  127. GuptaV.K. ScheunemannL. EisenbergT. MertelS. BhukelA. KoemansT.S. KramerJ.M. LiuK.S.Y. SchroederS. StunnenbergH.G. SinnerF. MagnesC. PieberT.R. DiptS. FialaA. SchenckA. SchwaerzelM. MadeoF. SigristS.J. Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner.Nat. Neurosci.201316101453146010.1038/nn.351223995066
     [Google Scholar]
  128. KruseN. PerssonS. AlcoleaD. BahlJ.M.C. BaldeirasI. CapelloE. ChiasseriniD. Bocchio ChiavettoL. EmersicA. EngelborghsS. ErenE. FladbyT. FrisoniG. García-AyllónM.S. GencS. GkatzimaO. HeegaardN.H.H. JaneiroA.M. KováčechB. KuiperijH.B. LeitãoM.J. LleóA. MartinsM. MatosM. MollergardH.M. NobiliF. ÖhrfeltA. ParnettiL. de OliveiraC.R. RotU. Sáez-ValeroJ. StruyfsH. TanassiJ.T. TaylorP. TsolakiM. VanmechelenE. VerbeekM.M. ZilkaN. BlennowK. ZetterbergH. MollenhauerB. Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study.Neurobiol. Aging20153692587259610.1016/j.neurobiolaging.2015.05.00326093515
     [Google Scholar]
  129. LiuD. PittaM. JiangH. LeeJ.H. ZhangG. ChenX. KawamotoE.M. MattsonM.P. Nicotinamide forestalls pathology and cognitive decline in Alzheimer mice: evidence for improved neuronal bioenergetics and autophagy procession.Neurobiol. Aging20133461564158010.1016/j.neurobiolaging.2012.11.02023273573
     [Google Scholar]
  130. GeislerJ.G. MarosiK. HalpernJ. MattsonM.P. DNP, mitochondrial uncoupling, and neuroprotection: A little dab’ll do ya.Alzheimers Dement.201713558259110.1016/j.jalz.2016.08.00127599210
     [Google Scholar]
  131. SpilmanP. PodlutskayaN. HartM.J. DebnathJ. GorostizaO. BredesenD. RichardsonA. StrongR. GalvanV. Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-β levels in a mouse model of Alzheimer’s disease.PLoS One201054e997910.1371/journal.pone.000997920376313
     [Google Scholar]
  132. TönniesE. TrushinaE. Oxidative stress, synaptic dysfunction, and Alzheimer’s disease.J. Alzheimers Dis.20175741105112110.3233/JAD‑16108828059794
     [Google Scholar]
  133. CheignonC. TomasM. Bonnefont-RousselotD. FallerP. HureauC. CollinF. Oxidative stress and the amyloid beta peptide in Alzheimer’s disease.Redox Biol.20181445046410.1016/j.redox.2017.10.01429080524
     [Google Scholar]
  134. BarnhamK.J. BushA.I. Biological metals and metal-targeting compounds in major neurodegenerative diseases.Chem. Soc. Rev.201443196727674910.1039/C4CS00138A25099276
     [Google Scholar]
  135. DumontM. KipianiK. YuF. WilleE. KatzM. CalingasanN.Y. GourasG.K. LinM.T. BealM.F. Coenzyme Q10 decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer’s disease.J. Alzheimers Dis.201127121122310.3233/JAD‑2011‑11020921799249
     [Google Scholar]
  136. GugliandoloA. BramantiP. MazzonE. Role of vitamin E in the treatment of Alzheimer’s disease: Evidence from animal models.Int. J. Mol. Sci.20171812250410.3390/ijms1812250429168797
     [Google Scholar]
  137. McManusM.J. MurphyM.P. FranklinJ.L. The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease.J. Neurosci.20113144157031571510.1523/JNEUROSCI.0552‑11.201122049413
     [Google Scholar]
  138. OliverD.M.A. ReddyP.H. Small molecules as therapeutic drugs for Alzheimer’s disease.Mol. Cell. Neurosci.201996476210.1016/j.mcn.2019.03.00130877034
     [Google Scholar]
  139. WebbM. SiderisD.P. BiddleM. Modulation of mitochondrial dysfunction for treatment of disease.Bioorg. Med. Chem. Lett.201929111270127710.1016/j.bmcl.2019.03.04130954429
     [Google Scholar]
  140. El-HattabA.W. ZaranteA.M. AlmannaiM. ScagliaF. Therapies for mitochondrial diseases and current clinical trials.Mol. Genet. Metab.201712231910.1016/j.ymgme.2017.09.00928943110
     [Google Scholar]
  141. OnyangoI. Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer’s disease.Neural Regen. Res.2018131192510.4103/1673‑5374.22436229451200
     [Google Scholar]
  142. ChenQ. PriorM. DarguschR. RobertsA. RiekR. EichmannC. ChirutaC. AkaishiT. AbeK. MaherP. SchubertD. A novel neurotrophic drug for cognitive enhancement and Alzheimer’s disease.PLoS One2011612e2786510.1371/journal.pone.002786522194796
     [Google Scholar]
  143. CurraisA. GoldbergJ. FarrokhiC. ChangM. PriorM. DarguschR. DaughertyD. ArmandoA. QuehenbergerO. MaherP. SchubertD. A comprehensive multiomics approach toward understanding the relationship between aging and dementia.Aging (Albany NY)201571193795510.18632/aging.10083826564964
     [Google Scholar]
  144. GoldbergJ. CurraisA. PriorM. FischerW. ChirutaC. RatliffE. DaughertyD. DarguschR. FinleyK. Esparza-MoltóP.B. CuezvaJ.M. MaherP. PetrascheckM. SchubertD. The mitochondrial ATP synthase is a shared drug target for aging and dementia.Aging Cell2018172e1271510.1111/acel.1271529316249
     [Google Scholar]
  145. ChakravortyA. JettoC.T. ManjithayaR. Dysfunctional mitochondria and mitophagy as drivers of Alzheimer’s disease pathogenesis.Front. Aging Neurosci.20191131110.3389/fnagi.2019.0031131824296
     [Google Scholar]
  146. ChengH. ShangY. JiangL. ShiT. WangL. The peroxisome proliferators activated receptor-gamma agonists as therapeutics for the treatment of Alzheimer’s disease and mild-to-moderate Alzheimer’s disease: a meta-analysis.Int. J. Neurosci.2016126429930710.3109/00207454.2015.101572226001206
     [Google Scholar]
  147. GalimbertiD. ScarpiniE. Pioglitazone for the treatment of Alzheimer’s disease.Expert Opin. Investig. Drugs20172619710110.1080/13543784.2017.126550427885860
     [Google Scholar]
  148. HamanoT. ShirafujiN. MakinoC. YenS.H. KanaanN.M. UenoA. SuzukiJ. IkawaM. MatsunagaA. YamamuraO. KuriyamaM. NakamotoY. Pioglitazone prevents tau oligomerization.Biochem. Biophys. Res. Commun.201647831035104210.1016/j.bbrc.2016.08.01627543203
     [Google Scholar]
  149. SatoT. HanyuH. HiraoK. KanetakaH. SakuraiH. IwamotoT. Efficacy of PPAR-γ agonist pioglitazone in mild Alzheimer disease.Neurobiol. Aging20113291626163310.1016/j.neurobiolaging.2009.10.00919923038
     [Google Scholar]
  150. RotermundC. MachetanzG. FitzgeraldJ.C. The therapeutic potential of metformin in neurodegenerative diseases.Front. Endocrinol. (Lausanne)2018940010.3389/fendo.2018.0040030072954
     [Google Scholar]
  151. OyenihiO.R. Antidiabetic effects of resveratrol: the way forward in its clinical utility.J. diabetes res.20162016973748310.1155/2016/9737483
     [Google Scholar]
  152. PallàsM. CasadesúsG. SmithM. Coto-MontesA. PelegriC. VilaplanaJ. CaminsA. Resveratrol and neurodegenerative diseases: activation of SIRT1 as the potential pathway towards neuroprotection.Curr. Neurovasc. Res.200961708110.2174/15672020978746601919355928
     [Google Scholar]
  153. UmJ.H. ParkS.J. KangH. YangS. ForetzM. McBurneyM.W. KimM.K. ViolletB. ChungJ.H. AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol.Diabetes201059355456310.2337/db09‑048219934007
     [Google Scholar]
  154. GuidaN. LaudatiG. AnzilottiS. SecondoA. MontuoriP. Di RenzoG. CanzonieroL.M.T. FormisanoL. Resveratrol via sirtuin-1 downregulates RE1-silencing transcription factor (REST) expression preventing PCB-95-induced neuronal cell death.Toxicol. Appl. Pharmacol.2015288338739810.1016/j.taap.2015.08.01026307266
     [Google Scholar]
  155. WangR. ZhangY. LiJ. ZhangC. Resveratrol ameliorates spatial learning memory impairment induced by Aβ 1–42 in rats.Neuroscience2017344394710.1016/j.neuroscience.2016.08.05127600946
     [Google Scholar]
/content/journals/cdth/10.2174/0115748855291425240802100148
Loading
Enhancing Mitochondrial Function: A Novel Therapeutic Target for Alzheimer's Disease
Curr Drug Ther 20, 1061 (2025); https://doi.org/10.2174/0115748855291425240802100148
/content/journals/cdth/10.2174/0115748855291425240802100148
/content/journals/cdth/10.2174/0115748855291425240802100148
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Alzheimer's disease; bioenergetics; mitochondrial dynamics; mitophagy; oxidative stress; β-amyloid

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test