Abstract
Neurodegenerative disease is an umbrella term for a range of pathological conditions primarily characterized by the progressive dysfunction and loss of selective neuronal populations. Bereft of cure and effective disease-modifying therapies, why and how this selective neuronal loss occurs in neurodegenerative diseases remain as the most intriguing and still unsolved questions in the field. Despite this limited knowledge regarding the trigger(s) underlying the different neurodegenerative phenotypes, during the last decades, mitochondrial dysfunction emerged as a common pathological feature being considered a “convergence point” for neurodegeneration. This is not surprising taking into account that neurons are post-mitotic cells with a complex architecture, long lifespan, and energetic requirements that fluctuate in time and space making them particularly reliant on a functional and dynamic mitochondrial network. Within this scenario, the present chapter provides an overview on the role of mitochondrial pathobiology in Alzheimer, Parkinson and Huntington diseases, the most prevalent neurodegenerative diseases. A more comprehensive view on the fundamental role of mitochondrial (mal)function during the pathological course of the abovementioned diseases may offer a new therapeutic window of opportunity to tackle the neurodegenerative phenotypes by bolstering mitochondrial health.
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Ali SF, David SN, Newport GD, Cadet JL, Slikker W Jr (1994) MPTP-induced oxidative stress and neurotoxicity are age-dependent: evidence from measures of reactive oxygen species and striatal dopamine levels. Synapse 18(1):27–34. https://doi.org/10.1002/syn.890180105
Atamna H (2006) Heme binding to Amyloid-beta peptide: mechanistic role in Alzheimer's disease. J Alzheimers Disease 10(2–3):255–266
Atamna H, Frey WH 2nd (2004) A role for heme in Alzheimer's disease: heme binds amyloid beta and has altered metabolism. Proc Natl Acad Sci U S A 101(30):11153–11158. https://doi.org/10.1073/pnas.0404349101
Autere J, Moilanen JS, Finnila S, Soininen H, Mannermaa A, Hartikainen P, Hallikainen M, Majamaa K (2004) Mitochondrial DNA polymorphisms as risk factors for Parkinson’s disease and Parkinson’s disease dementia. Hum Genet 115(1):29–35. https://doi.org/10.1007/s00439-004-1123-9
Bales KR (2004) Neurodegenerative disease research in the 21st century. Drug Discov Today 9(13):553–556. https://doi.org/10.1016/S1359-6446(04)03120-4
Baloyannis SJ (2006) Mitochondrial alterations in Alzheimer's disease. J Alzheimers Disease 9(2):119–126
Barroso N, Campos Y, Huertas R, Esteban J, Molina JA, Alonso A, Gutierrez-Rivas E, Arenas J (1993) Respiratory chain enzyme activities in lymphocytes from untreated patients with Parkinson disease. Clin Chem 39(4):667–669
Bates GP (2005) History of genetic disease: the molecular genetics of Huntington disease - a history. Nat Rev Genet 6(10):766–773
Beal MF, Brouillet E, Jenkins BG, Ferrante RJ, Kowall NW, Miller JM, Storey E, Srivastava R, Rosen BR, Hyman BT (1993) Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J Neurosci 13(10):4181–4192
Berardelli A, Wenning GK, Antonini A, Berg D, Bloem BR, Bonifati V, Brooks D, Burn DJ, Colosimo C, Fanciulli A, Ferreira J, Gasser T, Grandas F, Kanovsky P, Kostic V, Kulisevsky J, Oertel W, Poewe W, Reese JP, Relja M, Ruzicka E, Schrag A, Seppi K, Taba P, Vidailhet M (2013) EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson's disease. Eur J Neurol 20(1):16–34. https://doi.org/10.1111/ene.12022
Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3(12):1301–1306
Blandini F, Nappi G, Greenamyre JT (1998) Quantitative study of mitochondrial complex I in platelets of parkinsonian patients. Mov Disord 13(1):11–15
Bose A, Beal MF (2016) Mitochondrial dysfunction in Parkinson’s disease. J Neurochem 139(Suppl 1):216–231. https://doi.org/10.1111/jnc.13731
Bossy-Wetzel E, Petrilli A, Knott AB (2008) Mutant huntingtin and mitochondrial dysfunction. Trends Neurosci 31(12):609–616
Braak H, Braak E (1995) Staging of Alzheimer’s disease-related neurofibrillary changes. Neurobiol Aging 16(3):271–278. discussion 278-284
Browne SE, Bowling AC, MacGarvey U, Baik MJ, Berger SC, Muqit MM, Bird ED, Beal MF (1997) Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia. Ann Neurol 41(5):646–653. https://doi.org/10.1002/ana.410410514
Bubber P, Haroutunian V, Fisch G, Blass JP, Gibson GE (2005) Mitochondrial abnormalities in Alzheimer brain: mechanistic implications. Ann Neurol 57(5):695–703. https://doi.org/10.1002/ana.20474
Calkins MJ, Reddy PH (2011) Amyloid beta impairs mitochondrial anterograde transport and degenerates synapses in Alzheimer’s disease neurons. Biochim Biophys Acta 1812(4):507–513. https://doi.org/10.1016/j.bbadis.2011.01.007
Calkins MJ, Manczak M, Mao P, Shirendeb U, Reddy PH (2011) 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 20(23):4515–4529. https://doi.org/10.1093/hmg/ddr381
Carvalho C, Correia SC, Cardoso S, Placido AI, Candeias E, Duarte AI, Moreira PI (2015) The role of mitochondrial disturbances in Alzheimer, Parkinson and Huntington diseases. Expert Rev Neurother 15(8):867–884. https://doi.org/10.1586/14737175.2015.1058160
Caspersen C, Wang N, Yao J, Sosunov A, Chen X, Lustbader JW, Xu HW, Stern D, McKhann G, Yan SD (2005) Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer’s disease. FASEB J 19(14):2040–2041. https://doi.org/10.1096/fj.05-3735fje
Celsi F, Pizzo P, Brini M, Leo S, Fotino C, Pinton P, Rizzuto R (2009) Mitochondria, calcium and cell death: a deadly triad in neurodegeneration. Biochim Biophys Acta 1787(5):335–344. https://doi.org/10.1016/j.bbabio.2009.02.021
Chang DT, Rintoul GL, Pandipati S, Reynolds IJ (2006) Mutant huntingtin aggregates impair mitochondrial movement and trafficking in cortical neurons. Neurobiol Dis 22(2):388–400. https://doi.org/10.1016/j.nbd.2005.12.007
Chinta SJ, Andersen JK (2008) Redox imbalance in Parkinson’s disease. Biochim Biophys Acta 1780(11):1362–1367
Cho DH, Nakamura T, Fang J, Cieplak P, Godzik A, Gu Z, Lipton SA (2009) S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury. Science 324(5923):102–105. https://doi.org/10.1126/science.1171091
Choo YS, Johnson GV, MacDonald M, Detloff PJ, Lesort M (2004) Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release. Hum Mol Genet 13(14):1407–1420. https://doi.org/10.1093/hmg/ddh162
Choong CJ, Mochizuki H (2017) Inappropriate trafficking of damaged mitochondria in Parkinson's disease. Stem Cell Investig 4:17. https://doi.org/10.21037/sci.2017.02.07
Chou JL, Shenoy DV, Thomas N, Choudhary PK, Laferla FM, Goodman SR, Breen GA (2011) Early dysregulation of the mitochondrial proteome in a mouse model of Alzheimer’s disease. J Proteome 74(4):466–479. https://doi.org/10.1016/j.jprot.2010.12.012
Ciron C, Zheng L, Bobela W, Knott GW, Leone TC, Kelly DP, Schneider BL (2015) PGC-1alpha activity in nigral dopamine neurons determines vulnerability to alpha-synuclein. Acta Neuropathol Commun 3:16. https://doi.org/10.1186/s40478-015-0200-8
Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441(7097):1162–1166. https://doi.org/10.1038/nature04779
Correia SC, Santos RX, Cardoso S, Carvalho C, Candeias E, Duarte AI, Placido AI, Santos MS, Moreira PI (2012a) Alzheimer disease as a vascular disorder: where do mitochondria fit? Exp Gerontol 47(11):878–886. https://doi.org/10.1016/j.exger.2012.07.006
Correia SC, Santos RX, Perry G, Zhu X, Moreira PI, Smith MA (2012b) Mitochondrial importance in Alzheimer’s, Huntington’s and Parkinson’s diseases. Adv Exp Med Biol 724:205–221. https://doi.org/10.1007/978-1-4614-0653-2_16
Correia SC, Perry G, Moreira PI (2016) Mitochondrial traffic jams in Alzheimer’s disease - pinpointing the roadblocks. Biochim Biophys Acta 1862(10):1909–1917. https://doi.org/10.1016/j.bbadis.2016.07.010
Covarrubias-Pinto A, Moll P, Solis-Maldonado M, Acuna AI, Riveros A, Miro MP, Papic E, Beltran FA, Cepeda C, Concha II, Brauchi S, Castro MA (2015) Beyond the redox imbalance: oxidative stress contributes to an impaired GLUT3 modulation in Huntington’s disease. Free Radic Biol Med 89:1085–1096. https://doi.org/10.1016/j.freeradbiomed.2015.09.024
Crouch PJ, Blake R, Duce JA, Ciccotosto GD, Li QX, Barnham KJ, Curtain CC, Cherny RA, Cappai R, Dyrks T, Masters CL, Trounce IA (2005) Copper-dependent inhibition of human cytochrome c oxidase by a dimeric conformer of amyloid-beta1-42. J Neurosci 25(3):672–679. https://doi.org/10.1523/JNEUROSCI.4276-04.2005
Cui L, Jeong H, Borovecki F, Parkhurst CN, Tanese N, Krainc D (2006) Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 127(1):59–69. https://doi.org/10.1016/j.cell.2006.09.015
Damiano M, Diguet E, Malgorn C, D'Aurelio M, Galvan L, Petit F, Benhaim L, Guillermier M, Houitte D, Dufour N, Hantraye P, Canals JM, Alberch J, Delzescaux T, Deglon N, Beal MF, Brouillet E (2013) A role of mitochondrial complex II defects in genetic models of Huntington’s disease expressing N-terminal fragments of mutant huntingtin. Hum Mol Genet 22(19):3869–3882. https://doi.org/10.1093/hmg/ddt242
Deng H, Dodson MW, Huang H, Guo M (2008) The Parkinson’s disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci U S A 105(38):14503–14508. https://doi.org/10.1073/pnas.0803998105
Devi L, Prabhu BM, Galati DF, Avadhani NG, Anandatheerthavarada HK (2006) Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer’s disease brain is associated with mitochondrial dysfunction. J Neurosci 26(35):9057–9068. https://doi.org/10.1523/JNEUROSCI.1469-06.2006
Du H, Guo L, Yan S, Sosunov AA, McKhann GM, Yan SS (2010) Early deficits in synaptic mitochondria in an Alzheimer’s disease mouse model. Proc Natl Acad Sci U S A 107(43):18670–18675. https://doi.org/10.1073/pnas.1006586107
Dugger BN, Dickson DW (2017) Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol 9(7). https://doi.org/10.1101/cshperspect.a028035
Durcan TM, Fon EA (2015) The three 'P's of mitophagy: PARKIN, PINK1, and post-translational modifications. Genes Dev 29(10):989–999. https://doi.org/10.1101/gad.262758.115
Ebneth A, Godemann R, Stamer K, Illenberger S, Trinczek B, Mandelkow E (1998) Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer’s disease. J Cell Biol 143(3):777–794
Ekstrand MI, Terzioglu M, Galter D, Zhu S, Hofstetter C, Lindqvist E, Thams S, Bergstrand A, Hansson FS, Trifunovic A, Hoffer B, Cullheim S, Mohammed AH, Olson L, Larsson NG (2007) Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons. Proc Natl Acad Sci U S A 104(4):1325–1330
Federico A, Cardaioli E, Da Pozzo P, Formichi P, Gallus GN, Radi E (2012) Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci 322(1–2):254–262. https://doi.org/10.1016/j.jns.2012.05.030
Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408(6809):239–247. https://doi.org/10.1038/35041687
Forno LS (1996) Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol 55(3):259–272
Franco-Iborra S, Vila M, Perier C (2016) The Parkinson disease mitochondrial hypothesis: where are we at? Neuroscientist 22(3):266–277. https://doi.org/10.1177/1073858415574600
Friedland RP, Jagust WJ, Huesman RH, Koss E, Knittel B, Mathis CA, Ober BA, Mazoyer BM, Budinger TF (1989) Regional cerebral glucose transport and utilization in Alzheimer’s disease. Neurology 39(11):1427–1434
Gan X, Huang S, Wu L, Wang Y, Hu G, Li G, Zhang H, Yu H, Swerdlow RH, Chen JX, Yan SS (2014) Inhibition of ERK-DLP1 signaling and mitochondrial division alleviates mitochondrial dysfunction in Alzheimer’s disease cybrid cell. Biochim Biophys Acta 1842(2):220–231. https://doi.org/10.1016/j.bbadis.2013.11.009
Gao J, Wang L, Liu J, Xie F, Su B, Wang X (2017) Abnormalities of mitochondrial dynamics in neurodegenerative diseases. Antioxidants (Basel) 6(2). https://doi.org/10.3390/antiox6020025
Gash DM, Rutland K, Hudson NL, Sullivan PG, Bing G, Cass WA, Pandya JD, Liu M, Choi DY, Hunter RL, Gerhardt GA, Smith CD, Slevin JT, Prince TS (2008) Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity. Ann Neurol 63(2):184–192
Gauthier LR, Charrin BC, Borrell-Pages M, Dompierre JP, Rangone H, Cordelieres FP, De Mey J, MacDonald ME, Lessmann V, Humbert S, Saudou F (2004) Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell 118(1):127–138. https://doi.org/10.1016/j.cell.2004.06.018
Geisler S, Holmstrom KM, Treis A, Skujat D, Weber SS, Fiesel FC, Kahle PJ, Springer W (2010) The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations. Autophagy 6(7):871–878
Gil JM, Rego AC (2008) Mechanisms of neurodegeneration in Huntington’s disease. Eur J Neurosci 27(11):2803–2820. https://doi.org/10.1111/j.1460-9568.2008.06310.x
Goldman JG, Postuma R (2014) Premotor and nonmotor features of Parkinson’s disease. Curr Opin Neurol 27(4):434–441. https://doi.org/10.1097/WCO.0000000000000112
Grimm A, Eckert A (2017) Brain aging and neurodegeneration: from a mitochondrial point of view. J Neurochem 143(4):418–431. https://doi.org/10.1111/jnc.14037
Gu M, Gash MT, Mann VM, Javoy-Agid F, Cooper JM, Schapira AH (1996) Mitochondrial defect in Huntington’s disease caudate nucleus. Ann Neurol 39(3):385–389. https://doi.org/10.1002/ana.410390317
Guardia-Laguarta C, Area-Gomez E, Rub C, Liu Y, Magrane J, Becker D, Voos W, Schon EA, Przedborski S (2014) alpha-Synuclein is localized to mitochondria-associated ER membranes. J Neurosci 34(1):249–259. https://doi.org/10.1523/JNEUROSCI.2507-13.2014
Guedes-Dias P, de Proenca J, Soares TR, Leitao-Rocha A, Pinho BR, Duchen MR, Oliveira JM (2015) HDAC6 inhibition induces mitochondrial fusion, autophagic flux and reduces diffuse mutant huntingtin in striatal neurons. Biochim Biophys Acta 1852(11):2484–2493. https://doi.org/10.1016/j.bbadis.2015.08.012
Guedes-Dias P, Pinho BR, Soares TR, de Proenca J, Duchen MR, Oliveira JM (2016) Mitochondrial dynamics and quality control in Huntington’s disease. Neurobiol Dis 90:51–57. https://doi.org/10.1016/j.nbd.2015.09.008
Guidetti P, Charles V, Chen EY, Reddy PH, Kordower JH, Whetsell WO Jr, Schwarcz R, Tagle DA (2001) Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production. Exp Neurol 169(2):340–350. https://doi.org/10.1006/exnr.2000.7626
Haas RH, Nasirian F, Nakano K, Ward D, Pay M, Hill R, Shults CW (1995) Low platelet mitochondrial complex I and complex II/III activity in early untreated Parkinson’s disease. Ann Neurol 37(6):714–722
Haun F, Nakamura T, Shiu AD, Cho DH, Tsunemi T, Holland EA, La Spada AR, Lipton SA (2013) S-nitrosylation of dynamin-related protein 1 mediates mutant huntingtin-induced mitochondrial fragmentation and neuronal injury in Huntington’s disease. Antioxid Redox Signal 19(11):1173–1184. https://doi.org/10.1089/ars.2012.4928
Hansson Petersen CA, Alikhani N, Behbahani H, Wiehager B, Pavlov PF, Alafuzoff I, Leinonen V, Ito A, Winblad B, Glaser E, Ankarcrona M (2008) The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci U S A 105(35):13145–13150. https://doi.org/10.1073/pnas.0806192105
Haylett W, Swart C, van der Westhuizen F, van Dyk H, van der Merwe L, van der Merwe C, Loos B, Carr J, Kinnear C, Bardien S (2016) Altered mitochondrial respiration and other features of mitochondrial function in parkin-mutant fibroblasts from Parkinson’disease patients. Parkinsons Dis 2016:1819209. https://doi.org/10.1155/2016/1819209
Hering T, Birth N, Taanman JW, Orth M (2015) Selective striatal mtDNA depletion in end-stage Huntington's disease R6/2 mice. Exp Neurol 266:22–29. https://doi.org/10.1016/j.expneurol.2015.02.004
Herrup K (2015) The case for rejecting the amyloid cascade hypothesis. Nat Neurosci 18(6):794–799. https://doi.org/10.1038/nn.4017
Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PL, Jones PK, Petersen RB, Perry G, Smith MA (2001) Mitochondrial abnormalities in Alzheimer’s disease. J Neurosci 21(9):3017–3023
Hollenbeck PJ, Saxton WM (2005) The axonal transport of mitochondria. J Cell Sci 118(Pt 23):5411–5419. https://doi.org/10.1242/jcs.02745
Hsieh CH, Shaltouki A, Gonzalez AE, Bettencourt da Cruz A, Burbulla LF, St Lawrence E, Schule B, Krainc D, Palmer TD, Wang X (2016) Functional impairment in miro degradation and mitophagy is a shared feature in familial and sporadic Parkinson’s disease. Cell Stem Cell 19(6):709–724. https://doi.org/10.1016/j.stem.2016.08.002
Hsu LJ, Sagara Y, Arroyo A, Rockenstein E, Sisk A, Mallory M, Wong J, Takenouchi T, Hashimoto M, Masliah E (2000) Alpha-synuclein promotes mitochondrial deficit and oxidative stress. Am J Pathol 157(2):401–410
Jagust WJ, Seab JP, Huesman RH, Valk PE, Mathis CA, Reed BR, Coxson PG, Budinger TF (1991) Diminished glucose transport in Alzheimer's disease: dynamic PET studies. J Cereb Blood Flow Metab 11(2):323–330. https://doi.org/10.1038/jcbfm.1991.65
Jellinger KA (2009) Recent advances in our understanding of neurodegeneration. J Neural Transm 116(9):1111–1162. https://doi.org/10.1007/s00702-009-0240-y
Jellinger KA (2010) Basic mechanisms of neurodegeneration: a critical update. J Cell Mol Med 14(3):457–487. https://doi.org/10.1111/j.1582-4934.2010.01010.x
Kane LA, Lazarou M, Fogel AI, Li Y, Yamano K, Sarraf SA, Banerjee S, Youle RJ (2014) PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol 205(2):143–153. https://doi.org/10.1083/jcb.201402104
Kann O, Kovacs R (2007) Mitochondria and neuronal activity. Am J Physiol Cell Physiol 292(2):C641–C657. https://doi.org/10.1152/ajpcell.00222.2006
Karran E, Mercken M, De Strooper B (2011) The amyloid cascade hypothesis for Alzheimer’s disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov 10(9):698–712. https://doi.org/10.1038/nrd3505
Khalil B, El Fissi N, Aouane A, Cabirol-Pol MJ, Rival T, Lievens JC (2015) PINK1-induced mitophagy promotes neuroprotection in Huntington’s disease. Cell Death Dis 6:e1617. https://doi.org/10.1038/cddis.2014.581
Kieburtz K (2016) Treating neurodegenerative disease before illness: a challenge for the 21st century. Lancet Neurol 15(6):540–541. https://doi.org/10.1016/S1474-4422(16)30001-1
Kim J, Moody JP, Edgerly CK, Bordiuk OL, Cormier K, Smith K, Beal MF, Ferrante RJ (2010) Mitochondrial loss, dysfunction and altered dynamics in Huntington’s disease. Hum Mol Genet 19(20):3919–3935. https://doi.org/10.1093/hmg/ddq306
Kim GH, Kim JE, Rhie SJ, Yoon S (2015) The role of oxidative stress in neurodegenerative diseases. Exp Neurobiol 24(4):325–340. https://doi.org/10.5607/en.2015.24.4.325
Koroshetz WJ, Jenkins BG, Rosen BR, Beal MF (1997) Energy metabolism defects in Huntington’s disease and effects of coenzyme Q10. Ann Neurol 41(2):160–165. https://doi.org/10.1002/ana.410410206
Kovari E, Horvath J, Bouras C (2009) Neuropathology of Lewy body disorders. Brain Res Bull 80(4–5):203–210. https://doi.org/10.1016/j.brainresbull.2009.06.018
Krige D, Carroll MT, Cooper JM, Marsden CD, Schapira AH (1992) Platelet mitochondrial function in Parkinson’s disease. The Royal Kings and Queens Parkinson Disease Research Group. Ann Neurol 32(6):782–788
Kuhl DE, Phelps ME, Markham CH, Metter EJ, Riege WH, Winter J (1982) Cerebral metabolism and atrophy in Huntington’s disease determined by 18FDG and computed tomographic scan. Ann Neurol 12(5):425–434. https://doi.org/10.1002/ana.410120504
Kuwert T, Lange HW, Langen KJ, Herzog H, Aulich A, Feinendegen LE (1989) Cerebral glucose consumption measured by PET in patients with and without psychiatric symptoms of Huntington’s disease. Psychiatry Res 29(3):361–362
Kwon SK, Hirabayashi Y, Polleux F (2016) Organelle-specific sensors for monitoring Ca2+ dynamics in neurons. Front Synaptic Neurosci 8:29. https://doi.org/10.3389/fnsyn.2016.00029
Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219(4587):979–980
Li XJ, Li SH, Sharp AH, Nucifora FC Jr, Schilling G, Lanahan A, Worley P, Snyder SH, Ross CA (1995) A huntingtin-associated protein enriched in brain with implications for pathology. Nature 378(6555):398–402. https://doi.org/10.1038/378398a0
Liang CL, Wang TT, Luby-Phelps K, German DC (2007) Mitochondria mass is low in mouse substantia nigra dopamine neurons: implications for Parkinson’s disease. Exp Neurol 203(2):370–380. https://doi.org/10.1016/j.expneurol.2006.08.015
Lin MY, Sheng ZH (2015) Regulation of mitochondrial transport in neurons. Exp Cell Res 334(1):35–44. https://doi.org/10.1016/j.yexcr.2015.01.004
Liot G, Bossy B, Lubitz S, Kushnareva Y, Sejbuk N, Bossy-Wetzel E (2009) Complex II inhibition by 3-NP causes mitochondrial fragmentation and neuronal cell death via an NMDA- and ROS-dependent pathway. Cell Death Differ 16(6):899–909
Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH (2006) Mitochondria are a direct site of A beta accumulation in Alzheimer’s disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet 15(9):1437–1449. https://doi.org/10.1093/hmg/ddl066
Martin-Maestro P, Gargini R, Perry G, Avila J, Garcia-Escudero V (2016) PARK2 enhancement is able to compensate mitophagy alterations found in sporadic Alzheimer’s disease. Hum Mol Genet 25(4):792–806. https://doi.org/10.1093/hmg/ddv616
Martin-Maestro P, Gargini R, AS A, Garcia E, Anton LC, Noggle S, Arancio O, Avila J, Garcia-Escudero V (2017) Mitophagy failure in fibroblasts and iPSC-derived neurons of Alzheimer’s disease-associated presenilin 1 mutation. Front Mol Neurosci 10:291. https://doi.org/10.3389/fnmol.2017.00291
Mastrogiacomo F, Bergeron C, Kish SJ (1993) Brain alpha-ketoglutarate dehydrogenase complex activity in Alzheimer’s disease. J Neurochem 61(6):2007–2014
McWilliams TG, Muqit MM (2017) PINK1 and Parkin: emerging themes in mitochondrial homeostasis. Curr Opin Cell Biol 45:83–91. https://doi.org/10.1016/j.ceb.2017.03.013
Moreira PI, Siedlak SL, Wang X, Santos MS, Oliveira CR, Tabaton M, Nunomura A, Szweda LI, Aliev G, Smith MA, Zhu X, Perry G (2007a) Autophagocytosis of mitochondria is prominent in Alzheimer disease. J Neuropathol Exp Neurol 66(6):525–532. https://doi.org/10.1097/01.jnen.0000240476.73532.b0
Moreira PI, Siedlak SL, Wang X, Santos MS, Oliveira CR, Tabaton M, Nunomura A, Szweda LI, Aliev G, Smith MA, Zhu X, Perry G (2007b) Increased autophagic degradation of mitochondria in Alzheimer disease. Autophagy 3(6):614–615
Moreira PI, Zhu X, Wang X, Lee HG, Nunomura A, Petersen RB, Perry G, Smith MA (2010) Mitochondria: a therapeutic target in neurodegeneration. Biochim Biophys Acta 1802(1):212–220. https://doi.org/10.1016/j.bbadis.2009.10.007
Mortiboys H, Johansen KK, Aasly JO, Bandmann O (2010) Mitochondrial impairment in patients with Parkinson disease with the G2019S mutation in LRRK2. Neurology 75(22):2017–2020. https://doi.org/10.1212/WNL.0b013e3181ff9685
Muangpaisan W, Mathews A, Hori H, Seidel D (2011) A systematic review of the worldwide prevalence and incidence of Parkinson’s disease. J Med Assoc Thai 94(6):749–755
Mutisya EM, Bowling AC, Beal MF (1994) Cortical cytochrome oxidase activity is reduced in Alzheimer’s disease. J Neurochem 63(6):2179–2184
Naia L, Ferreira IL, Ferreiro E, Rego AC (2017) Mitochondrial Ca2+ handling in Huntington’s and Alzheimer’s diseases - role of ER-mitochondria crosstalk. Biochem Biophys Res Commun 483(4):1069–1077. https://doi.org/10.1016/j.bbrc.2016.07.122
Narendra D, Tanaka A, Suen DF, Youle RJ (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183(5):795–803. https://doi.org/10.1083/jcb.200809125
Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, Jones PK, Ghanbari H, Wataya T, Shimohama S, Chiba S, Atwood CS, Petersen RB, Smith MA (2001) Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 60(8):759–767
Oliveira JM (2010) Nature and cause of mitochondrial dysfunction in Huntington's disease: focusing on huntingtin and the striatum. J Neurochem 114(1):1–12. https://doi.org/10.1111/j.1471-4159.2010.06741.x
Orr AL, Li S, Wang CE, Li H, Wang J, Rong J, Xu X, Mastroberardino PG, Greenamyre JT, Li XJ (2008) N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial trafficking. J Neurosci 28(11):2783–2792. https://doi.org/10.1523/JNEUROSCI.0106-08.2008
Panov AV, Gutekunst CA, Leavitt BR, Hayden MR, Burke JR, Strittmatter WJ, Greenamyre JT (2002) Early mitochondrial calcium defects in Huntington’s disease are a direct effect of polyglutamines. Nat Neurosci 5(8):731–736. https://doi.org/10.1038/nn884
Papkovskaia TD, Chau KY, Inesta-Vaquera F, Papkovsky DB, Healy DG, Nishio K, Staddon J, Duchen MR, Hardy J, Schapira AH, Cooper JM (2012) G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization. Hum Mol Genet 21(19):4201–4213. https://doi.org/10.1093/hmg/dds244
Parker WD Jr, Boyson SJ, Parks JK (1989) Abnormalities of the electron transport chain in idiopathic Parkinson’s disease. Ann Neurol 26(6):719–723
Parker WD Jr, Parks JK, Swerdlow RH (2008) Complex I deficiency in Parkinson’s disease frontal cortex. Brain Res 1189:215–218
Penn AM, Roberts T, Hodder J, Allen PS, Zhu G, Martin WR (1995) Generalized mitochondrial dysfunction in Parkinson’s disease detected by magnetic resonance spectroscopy of muscle. Neurology 45(11):2097–2099
Persson T, Popescu BO, Cedazo-Minguez A (2014) Oxidative stress in Alzheimer’s disease: why did antioxidant therapy fail? Oxidative Med Cell Longev 2014:427318. https://doi.org/10.1155/2014/427318
Polyzos AA, McMurray CT (2017) The chicken or the egg: mitochondrial dysfunction as a cause or consequence of toxicity in Huntington’s disease. Mech Ageing Dev 161(Pt A):181–197. https://doi.org/10.1016/j.mad.2016.09.003
Poole AC, Thomas RE, Andrews LA, McBride HM, Whitworth AJ, Pallanck LJ (2008) The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A 105(5):1638–1643. https://doi.org/10.1073/pnas.0709336105
Pozo Devoto VM, Dimopoulos N, Alloatti M, Pardi MB, Saez TM, Otero MG, Cromberg LE, Marin-Burgin A, Scassa ME, Stokin GB, Schinder AF, Sevlever G, Falzone TL (2017) alphaSynuclein control of mitochondrial homeostasis in human-derived neurons is disrupted by mutations associated with Parkinson’s disease. Sci Rep 7(1):5042. https://doi.org/10.1038/s41598-017-05334-9
Qin W, Haroutunian V, Katsel P, Cardozo CP, Ho L, Buxbaum JD, Pasinetti GM (2009) PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia. Arch Neurol 66(3):352–361. https://doi.org/10.1001/archneurol.2008.588
Querfurth HW, LaFerla FM (2010) Alzheimer’s disease. N Engl J Med 362(4):329–344. https://doi.org/10.1056/NEJMra0909142
Quintanilla RA, Dolan PJ, Jin YN, Johnson GV (2012) Truncated tau and Abeta cooperatively impair mitochondria in primary neurons. Neurobiol Aging 33(3):619.e625–619.e635. https://doi.org/10.1016/j.neurobiolaging.2011.02.007
Reddy PH, Reddy TP (2011) Mitochondria as a therapeutic target for aging and neurodegenerative diseases. Curr Alzheimer Res 8(4):393–409
Reiner A, Albin RL, Anderson KD, D'Amato CJ, Penney JB, Young AB (1988) Differential loss of striatal projection neurons in Huntington disease. Proc Natl Acad Sci U S A 85(15):5733–5737
Resende R, Moreira PI, Proenca T, Deshpande A, Busciglio J, Pereira C, Oliveira CR (2008) Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease. Free Radic Biol Med 44(12):2051–2057. https://doi.org/10.1016/j.freeradbiomed.2008.03.012
Rhein V, Song X, Wiesner A, Ittner LM, Baysang G, Meier F, Ozmen L, Bluethmann H, Drose S, Brandt U, Savaskan E, Czech C, Gotz J, Eckert A (2009) Amyloid-beta and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer’s disease mice. Proc Natl Acad Sci U S A 106(47):20057–20062. https://doi.org/10.1073/pnas.0905529106
Rodolfo C, Campello S, Cecconi F (2017) Mitophagy in neurodegenerative diseases. Neurochem Int. https://doi.org/10.1016/j.neuint.2017.08.004
Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 54(3):823–827
Schapira AHV, Chaudhuri KR, Jenner P (2017) Non-motor features of Parkinson disease. Nat Rev Neurosci 18(7):435–450. https://doi.org/10.1038/nrn.2017.62
Seo AY, Joseph AM, Dutta D, Hwang JC, Aris JP, Leeuwenburgh C (2010) New insights into the role of mitochondria in aging: mitochondrial dynamics and more. J Cell Sci 123(Pt 15):2533–2542. https://doi.org/10.1242/jcs.070490
Shaerzadeh F, Motamedi F, Minai-Tehrani D, Khodagholi F (2014) Monitoring of neuronal loss in the hippocampus of Abeta-injected rat: autophagy, mitophagy, and mitochondrial biogenesis stand against apoptosis. NeuroMolecular Med 16(1):175–190. https://doi.org/10.1007/s12017-013-8272-8
Shah K, Desilva S, Abbruscato T (2012) The role of glucose transporters in brain disease: diabetes and Alzheimer’s disease. Int J Mol Sci 13(10):12629–12655. https://doi.org/10.3390/ijms131012629
Sheng ZH (2014) Mitochondrial trafficking and anchoring in neurons: new insight and implications. J Cell Biol 204(7):1087–1098. https://doi.org/10.1083/jcb.201312123
Sheng ZH, Cai Q (2012) Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration. Nat Rev Neurosci 13(2):77–93. https://doi.org/10.1038/nrn3156
Sheng B, Wang X, Su B, Lee HG, Casadesus G, Perry G, Zhu X (2012) Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer’s disease. J Neurochem 120(3):419–429. https://doi.org/10.1111/j.1471-4159.2011.07581.x
Sherer TB, Betarbet R, Stout AK, Lund S, Baptista M, Panov AV, Cookson MR, Greenamyre JT (2002) An in vitro model of Parkinson’s disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage. J Neurosci 22(16):7006–7015. doi:20026721
Sherer TB, Richardson JR, Testa CM, Seo BB, Panov AV, Yagi T, Matsuno-Yagi A, Miller GW, Greenamyre JT (2007) Mechanism of toxicity of pesticides acting at complex I: relevance to environmental etiologies of Parkinson’s disease. J Neurochem 100(6):1469–1479
Shin JH, Ko HS, Kang H, Lee Y, Lee YI, Pletinkova O, Troconso JC, Dawson VL, Dawson TM (2011) PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson’s disease. Cell 144(5):689–702. https://doi.org/10.1016/j.cell.2011.02.010
Shirendeb UP, Calkins MJ, Manczak M, Anekonda V, Dufour B, McBride JL, Mao P, Reddy PH (2012) Mutant huntingtin’s interaction with mitochondrial protein Drp1 impairs mitochondrial biogenesis and causes defective axonal transport and synaptic degeneration in Huntington’s disease. Hum Mol Genet 21(2):406–420. https://doi.org/10.1093/hmg/ddr475
Skovronsky DM, Lee VM, Trojanowski JQ (2006) Neurodegenerative diseases: new concepts of pathogenesis and their therapeutic implications. Annu Rev Pathol 1:151–170. https://doi.org/10.1146/annurev.pathol.1.110304.100113
Song W, Chen J, Petrilli A, Liot G, Klinglmayr E, Zhou Y, Poquiz P, Tjong J, Pouladi MA, Hayden MR, Masliah E, Ellisman M, Rouiller I, Schwarzenbacher R, Bossy B, Perkins G, Bossy-Wetzel E (2011) Mutant huntingtin binds the mitochondrial fission GTPase dynamin-related protein-1 and increases its enzymatic activity. Nat Med 17(3):377–382. https://doi.org/10.1038/nm.2313
Spillantini MG, Goedert M (2000) The alpha-synucleinopathies: Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Ann N Y Acad Sci 920:16–27
Squitieri F, Cannella M, Sgarbi G, Maglione V, Falleni A, Lenzi P, Baracca A, Cislaghi G, Saft C, Ragona G, Russo MA, Thompson LM, Solaini G, Fornai F (2006) Severe ultrastructural mitochondrial changes in lymphoblasts homozygous for Huntington disease mutation. Mech Ageing Dev 127(2):217–220
Stevens DA, Lee Y, Kang HC, Lee BD, Lee YI, Bower A, Jiang H, Kang SU, Andrabi SA, Dawson VL, Shin JH, Dawson TM (2015) Parkin loss leads to PARIS-dependent declines in mitochondrial mass and respiration. Proc Natl Acad Sci U S A 112(37):11696–11701. https://doi.org/10.1073/pnas.1500624112
Su YC, Qi X (2013) Inhibition of excessive mitochondrial fission reduced aberrant autophagy and neuronal damage caused by LRRK2 G2019S mutation. Hum Mol Genet 22(22):4545–4561. https://doi.org/10.1093/hmg/ddt301
Subramaniam SR, Chesselet MF (2013) Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Prog Neurobiol 106–107:17–32. https://doi.org/10.1016/j.pneurobio.2013.04.004
Sultana R, Butterfield DA (2013) Oxidative modification of brain proteins in Alzheimer’s disease: perspective on future studies based on results of redox proteomics studies. J Alzheimers Dis 33(Suppl 1):S243–S251. https://doi.org/10.3233/JAD-2012-129018
Swerdlow RH, Khan SM (2004) A “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease. Med Hypotheses 63(1):8–20. https://doi.org/10.1016/j.mehy.2003.12.045
Swerdlow RH, Parks JK, Miller SW, Tuttle JB, Trimmer PA, Sheehan JP, Bennett JP Jr, Davis RE, Parker WD Jr (1996) Origin and functional consequences of the complex I defect in Parkinson’s disease. Ann Neurol 40(4):663–671. https://doi.org/10.1002/ana.410400417
Swerdlow RH, Parks JK, Davis JN 2nd, Cassarino DS, Trimmer PA, Currie LJ, Dougherty J, Bridges WS, Bennett JP Jr, Wooten GF, Parker WD (1998) Matrilineal inheritance of complex I dysfunction in a multigenerational Parkinson’s disease family. Ann Neurol 44(6):873–881
Swerdlow RH, Burns JM, Khan SM (2014) The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives. Biochim Biophys Acta 1842(8):1219–1231. https://doi.org/10.1016/j.bbadis.2013.09.010
Taylor DJ, Krige D, Barnes PR, Kemp GJ, Carroll MT, Mann VM, Cooper JM, Marsden CD, Schapira AH (1994) A 31P magnetic resonance spectroscopy study of mitochondrial function in skeletal muscle of patients with Parkinson’s disease. J Neurol Sci 125(1):77–81
Tretter L, Adam-Vizi V (2000) Inhibition of Krebs cycle enzymes by hydrogen peroxide: a key role of [alpha]-ketoglutarate dehydrogenase in limiting NADH production under oxidative stress. J Neurosci 20(24):8972–8979
Trimmer PA, Borland MK (2005) Differentiated Alzheimer’s disease transmitochondrial cybrid cell lines exhibit reduced organelle movement. Antioxid Redox Signal 7(9–10):1101–1109. https://doi.org/10.1089/ars.2005.7.1101
Trushina E, Dyer RB, Badger JD 2nd, Ure D, Eide L, Tran DD, Vrieze BT, Legendre-Guillemin V, McPherson PS, Mandavilli BS, Van Houten B, Zeitlin S, McNiven M, Aebersold R, Hayden M, Parisi JE, Seeberg E, Dragatsis I, Doyle K, Bender A, Chacko C, McMurray CT (2004) Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol Cell Biol 24(18):8195–8209. https://doi.org/10.1128/MCB.24.18.8195-8209.2004
Utton MA, Noble WJ, Hill JE, Anderton BH, Hanger DP (2005) Molecular motors implicated in the axonal transport of tau and alpha-synuclein. J Cell Sci 118(Pt 20):4645–4654. https://doi.org/10.1242/jcs.02558
Veech GA, Dennis J, Keeney PM, Fall CP, Swerdlow RH, Parker WD Jr, Bennett JP Jr (2000) Disrupted mitochondrial electron transport function increases expression of anti-apoptotic bcl-2 and bcl-X(L) proteins in SH-SY5Y neuroblastoma and in Parkinson disease cybrid cells through oxidative stress. J Neurosci Res 61(6):693–700
Vos M, Lauwers E, Verstreken P (2010) Synaptic mitochondria in synaptic transmission and organization of vesicle pools in health and disease. Front Synaptic Neurosci 2:139. https://doi.org/10.3389/fnsyn.2010.00139
Vossel KA, Zhang K, Brodbeck J, Daub AC, Sharma P, Finkbeiner S, Cui B, Mucke L (2010) Tau reduction prevents Abeta-induced defects in axonal transport. Science 330(6001):198. https://doi.org/10.1126/science.1194653
Wang X, Su B, Lee HG, Li X, Perry G, Smith MA, Zhu X (2009) Impaired balance of mitochondrial fission and fusion in Alzheimer’s disease. J Neurosci 29(28):9090–9103. https://doi.org/10.1523/JNEUROSCI.1357-09.2009
Wang X, Perry G, Smith MA, Zhu X (2010) Amyloid-beta-derived diffusible ligands cause impaired axonal transport of mitochondria in neurons. Neurodegener Dis 7(1–3):56–59. https://doi.org/10.1159/000283484
Wang X, Su B, Liu W, He X, Gao Y, Castellani RJ, Perry G, Smith MA, Zhu X (2011a) DLP1-dependent mitochondrial fragmentation mediates 1-methyl-4-phenylpyridinium toxicity in neurons: implications for Parkinson’s disease. Aging Cell 10(5):807–823. https://doi.org/10.1111/j.1474-9726.2011.00721.x
Wang X, Winter D, Ashrafi G, Schlehe J, Wong YL, Selkoe D, Rice S, Steen J, LaVoie MJ, Schwarz TL (2011b) PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 147(4):893–906. https://doi.org/10.1016/j.cell.2011.10.018
Wang X, Petrie TG, Liu Y, Liu J, Fujioka H, Zhu X (2012a) Parkinson’s disease-associated DJ-1 mutations impair mitochondrial dynamics and cause mitochondrial dysfunction. J Neurochem 121(5):830–839. https://doi.org/10.1111/j.1471-4159.2012.07734.x
Wang X, Yan MH, Fujioka H, Liu J, Wilson-Delfosse A, Chen SG, Perry G, Casadesus G, Zhu X (2012b) LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1. Hum Mol Genet 21(9):1931–1944. https://doi.org/10.1093/hmg/dds003
Wang W, Wang X, Fujioka H, Hoppel C, Whone AL, Caldwell MA, Cullen PJ, Liu J, Zhu X (2016) Parkinson’s disease-associated mutant VPS35 causes mitochondrial dysfunction by recycling DLP1 complexes. Nat Med 22(1):54–63. https://doi.org/10.1038/nm.3983
Westermann B (2010) Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol 11(12):872–884. https://doi.org/10.1038/nrm3013
Weydt P, Pineda VV, Torrence AE, Libby RT, Satterfield TF, Lazarowski ER, Gilbert ML, Morton GJ, Bammler TK, Strand AD, Cui L, Beyer RP, Easley CN, Smith AC, Krainc D, Luquet S, Sweet IR, Schwartz MW, La Spada AR (2006) Thermoregulatory and metabolic defects in Huntington’s disease transgenic mice implicate PGC-1alpha in Huntington’s disease neurodegeneration. Cell Metab 4(5):349–362. https://doi.org/10.1016/j.cmet.2006.10.004
Wild P, Dikic I (2010) Mitochondria get a Parkin’ ticket. Nat Cell Biol 12(2):104–106. https://doi.org/10.1038/ncb0210-104
Wong YC, Holzbaur EL (2014) The regulation of autophagosome dynamics by huntingtin and HAP1 is disrupted by expression of mutant huntingtin, leading to defective cargo degradation. J Neurosci 34(4):1293–1305. https://doi.org/10.1523/JNEUROSCI.1870-13.2014
Xie W, Chung KK (2012) Alpha-synuclein impairs normal dynamics of mitochondria in cell and animal models of Parkinson’s disease. J Neurochem 122(2):404–414. https://doi.org/10.1111/j.1471-4159.2012.07769.x
Yamano K, Matsuda N, Tanaka K (2016) The ubiquitin signal and autophagy: an orchestrated dance leading to mitochondrial degradation. EMBO Rep 17(3):300–316. https://doi.org/10.15252/embr.201541486
Yao Z, Wood NW (2009) Cell death pathways in Parkinson’s disease: role of mitochondria. Antioxid Redox Signal 11(9):2135–2149. https://doi.org/10.1089/ARS.2009.2624
Yao J, Irwin RW, Zhao L, Nilsen J, Hamilton RT, Brinton RD (2009) Mitochondrial bioenergetic deficit precedes Alzheimer’s pathology in female mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A 106(34):14670–14675. https://doi.org/10.1073/pnas.0903563106
Ye X, Sun X, Starovoytov V, Cai Q (2015) Parkin-mediated mitophagy in mutant hAPP neurons and Alzheimer’s disease patient brains. Hum Mol Genet 24(10):2938–2951. https://doi.org/10.1093/hmg/ddv056
Yoshino H, Nakagawa-Hattori Y, Kondo T, Mizuno Y (1992) Mitochondrial complex I and II activities of lymphocytes and platelets in Parkinson’s disease. J Neural Transm Park Dis Dement Sect 4(1):27–34
Yue M, Hinkle KM, Davies P, Trushina E, Fiesel FC, Christenson TA, Schroeder AS, Zhang L, Bowles E, Behrouz B, Lincoln SJ, Beevers JE, Milnerwood AJ, Kurti A, McLean PJ, Fryer JD, Springer W, Dickson DW, Farrer MJ, Melrose HL (2015) Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice. Neurobiol Dis 78:172–195. https://doi.org/10.1016/j.nbd.2015.02.031
Zhang Z, Liu L, Jiang X, Zhai S, Xing D (2016) The essential role of Drp1 and its regulation by S-nitrosylation of parkin in dopaminergic neurodegeneration: implications for Parkinson’s disease. Antioxid Redox Signal 25(11):609–622. https://doi.org/10.1089/ars.2016.6634
Zheng B, Liao Z, Locascio JJ, Lesniak KA, Roderick SS, Watt ML, Eklund AC, Zhang-James Y, Kim PD, Hauser MA, Grunblatt E, Moran LB, Mandel SA, Riederer P, Miller RM, Federoff HJ, Wullner U, Papapetropoulos S, Youdim MB, Cantuti-Castelvetri I, Young AB, Vance JM, Davis RL, Hedreen JC, Adler CH, Beach TG, Graeber MB, Middleton FA, Rochet JC, Scherzer CR, Global PDGEC (2010) PGC-1alpha, a potential therapeutic target for early intervention in Parkinson’s disease. Sci Transl Med 2(52):52ra73. https://doi.org/10.1126/scitranslmed.3001059
Zhu J, Wang KZ, Chu CT (2013) After the banquet: mitochondrial biogenesis, mitophagy, and cell survival. Autophagy 9(11):1663–1676. https://doi.org/10.4161/auto.24135
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Correia, S.C., Moreira, P.I. (2018). Role of Mitochondria in Neurodegenerative Diseases: The Dark Side of the “Energy Factory”. In: Oliveira, P. (eds) Mitochondrial Biology and Experimental Therapeutics. Springer, Cham. https://doi.org/10.1007/978-3-319-73344-9_11
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