Skip to main content
SpringerLink
Log in

Mitochondria and Neurodegeneration

  • Original Paper
  • Published:
Bioscience Reports

Abstract

Many lines of evidence suggest that mitochondria have a central role in ageing-related neurodegenerative diseases. However, despite the evidence of morphological, biochemical and molecular abnormalities in mitochondria in various tissues of patients with neurodegenerative disorders, the question “is mitochondrial dysfunction a necessary step in neurodegeneration?” is still unanswered. In this review, we highlight some of the major neurodegenerative disorders (Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis and Huntington’s disease) and discuss the role of the mitochondria in the pathogenetic cascade leading to neurodegeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Afifi AK, Aleu FP, Goodgold J, MacKay B (1966) Ultrastructure of atrophic muscle in amyotrophic lateral sclerosis. Neurology 16:475–481

    PubMed  CAS  Google Scholar 

  • Anandatheerthavarada HK, Biswas G, Robin MA, Avadhani NG (2003) Mitochondrial targeting and a novel transmembrane arrest of Alzheimer’s amyloid precursor protein impairs mitochondrial function in neuronal cells. J Cell Biol 161:41–54

    Article  PubMed  CAS  Google Scholar 

  • Atsumi T (1981) The ultrastructure of intramuscular nerves in amyotrophic lateral sclerosis. Acta Neuropathol 55:193–198

    Article  PubMed  CAS  Google Scholar 

  • Autere J, 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 115:29–35

    Article  PubMed  CAS  Google Scholar 

  • Beal MF (2003) Bioenergetic approaches for neuroprotection in Parkinson’s disease. Ann Neurol 53:S39–S47

    Article  PubMed  CAS  Google Scholar 

  • Beal MF (2005) Mitochondria take center stage in aging and neurodegeneration. Ann Neurol 58:495–505

    Article  PubMed  CAS  Google Scholar 

  • Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, Taylor RW, Turnbull DM (2006) High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 38:515–517

    Article  PubMed  CAS  Google Scholar 

  • 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 3:1301–1306

    Article  PubMed  CAS  Google Scholar 

  • Betarbet R, Sherer TB, Greenamyre JT (2005) Ubiquitin–proteasome system and Parkinson’s diseases. Exp Neurol 191:S17–S27

    Article  PubMed  CAS  Google Scholar 

  • Bindoff LA, Birch-Machin M, Cartlidge NE, Parker WD Jr, Turnbull DM (1989) Mitochondrial function in Parkinson’s disease. Lancet 2:49

    Article  PubMed  CAS  Google Scholar 

  • Blass JP, Sheu RK, Gibson GE (2000) Inherent abnormalities in energy metabolism in Alzheimer disease. Interaction with cerebrovascular compromise. Ann NY Acad Sci 903:204–221

    Article  PubMed  CAS  Google Scholar 

  • Borthwick GM, Johnson MA, Ince PG, Shaw PJ, Turnbull DM (1999) Mitochondrial enzyme activity in amyotrophic lateral sclerosis: implications for the role of mitochondria in neuronal cell death. Ann Neurol 46:787–790

    Article  PubMed  CAS  Google Scholar 

  • Borthwick GM, Taylor RW, Walls TJ, Tonska K, Taylor GA, Shaw PJ, Ince PG, Turnbull DM (2006) Motor neuron disease in a patient with a mitochondrial tRNAIle mutation. Ann Neurol 59:570–574

    Article  PubMed  CAS  Google Scholar 

  • Bosetti F, Brizzi F, Barogi S, Mancuso M, Siciliano G, Tendi EA, Murri L, Rapoport SI, Solaini G (2002) Cytochrome c oxidase and mitochondrial F1F0–ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer’s disease. Neurobiol Aging 23:371–376

    Article  PubMed  CAS  Google Scholar 

  • Bowling AC, Schulz JB, Brown RH Jr, Beal MF (1993) Superoxide dismutase activity, oxidative damage, and mitochondrial energy metabolism in familial and sporadic amyotrophic lateral sclerosis. J Neurochem 61:2322–2325

    Article  PubMed  CAS  Google Scholar 

  • 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 41:646–53

    Article  PubMed  CAS  Google Scholar 

  • Browne SE, Yang L, DiMauro JP, Fuller SW, Licata SC, Beal MF (2006) Bioenergetic abnormalities in discrete cerebral motor pathways presage spinal cord pathology in the G93A SOD1 mouse model of ALS. Neurobiol Dis 22:599–610

    Article  PubMed  CAS  Google Scholar 

  • Bubber P, Haroutunian V, Fisch G, Blass JP, Gibson GE (2005) Mitochondrial abnormalities in Alzheimer brain: mechanistic implications. Ann Neurol 57:695–703

    Article  PubMed  CAS  Google Scholar 

  • Butterworth J, Yates CM, Reynolds GP (1985) Distribution of phosphate-activated glutaminase, succinic dehydrogenase, pyruvate dehydrogenase and gamma-glutamyl transpeptidase in post-mortem brain from Huntington’s disease and agonal cases. J Neurol Sci 67:161–171

    Article  PubMed  CAS  Google Scholar 

  • Cardoso SM, Proenca MT, Santos S, Santana I, Oliveira CR (2004a) Cytochrome c oxidase is decreased in Alzheimer’s disease platelets. Neurobiol Aging 25:105–110

    Article  PubMed  CAS  Google Scholar 

  • Cardoso SM, Santana I, Swerdlow RH, Oliveira CR (2004b) Mitochondria dysfunction of Alzheimer’s disease cybrids enhances Abeta toxicity. J Neurochem 89:1417–1426

    Article  PubMed  CAS  Google Scholar 

  • Casali C, Bonifati V, Santorelli FM, Casari G, Fortini D, Patrignani A, Fabbrini G, Carrozzo R, D’Amati G, Locuratolo N, Vanacore N, Damiano M, Pierallini A, Pierelli F, Amabile GA, Meco G (2001) Mitochondrial myopathy, parkinsonism, and multiple mtDNA deletions in a Sephardic Jewish family. Neurology 56:802–805

    PubMed  CAS  Google Scholar 

  • Castellani R, Hirai K, Aliev G, Drew KL, Nunomura A, Takeda A, Cash AD, Obrenovich ME, Perry G, Smith MA (2002) Role of mitochondrial dysfunction in Alzheimer’s disease. J Neurosci Res 70(3):357–360

    Article  PubMed  CAS  Google Scholar 

  • Chagnon P, Gee M, Filion M, Robitaille Y, Belouchi M, Gauvreau D (1999) Phylogenetic analysis of the mitochondrial genome indicates significant differences between patients with Alzheimer disease and controls in a French-Canadian founder population. Am J Med Genet 85:20–30

    Article  PubMed  CAS  Google Scholar 

  • Chalmers RM, Brockington M, Howard RS, Lecky BR, Morgan-Hughes JA, Harding AE (1996) Mitochondrial encephalopathy with multiple mitochondrial DNA deletions: a report of two families and two sporadic cases with unusual clinical and neuropathological features. J Neurol Sci 143:41–45

    Article  PubMed  CAS  Google Scholar 

  • Chinnery PF, Taylor GA, Howell N, Brown DT, Parsons TJ, Turnbull DM (2001) Point mutations of the mtDNA control region in normal and neurodegenerative human brains. Am J Hum Genet 68:529–532

    Article  PubMed  CAS  Google Scholar 

  • Chinnery PF, Mowbray C, Elliot H, Elson JL, Nixon H, Hartley J, Shaw PJ (2007) Mitochondrial DNA haplogroups and amyotrophic lateral sclerosis. Neurogenetics 8:65–67

    Article  PubMed  Google Scholar 

  • Comi GP, Bordoni A, Salani S, Franceschina L, Sciacco M, Prelle A, Fortunato F, Zeviani M, Napoli L, Bresolin N, Moggio M, Ausenda CD, Taanman JW, Scarlato G (1998) Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease. Ann Neurol 43:110–116

    Article  PubMed  CAS  Google Scholar 

  • Cooper JM, Daniel SE, Marsden CD, Schapira AH (1995) L-dihydroxyphenylalanine and complex I deficiency in Parkinson’s disease brain. Mov Disord 10:295–297

    Article  PubMed  CAS  Google Scholar 

  • Coskun PE, Beal MF, Wallace DC (2004) Alzheimer’s brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication. Proc Natl Acad Sci USA 101:10726–10731

    Article  PubMed  CAS  Google Scholar 

  • Crompton M (2004) Mitochondria and aging: a role for the permeability transition? Aging Cell 3:3–6

    Article  PubMed  CAS  Google Scholar 

  • 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 25:672–679

    Article  PubMed  CAS  Google Scholar 

  • Dal Canto MC, Gurney ME (1994) Development of central nervous system pathology in a murine transgenic model of human amyotrophic lateral sclerosis. Am J Pathol 145:1271–1279

    PubMed  CAS  Google Scholar 

  • Dal Canto MC (1995) Comparison of pathological alterations in ALS and a murine transgenic model: pathogenetic implications. Clin Neurosci 3:332–337

    PubMed  Google Scholar 

  • Damiano M, Starkov AA, Petri S, Kipiani K, Kiaei M, Mattiazzi M, Beal MF, Manfredi G (2006) Neural mitochondrial Ca2+ capacity impairment precedes the onset of motor symptoms in G93A Cu/Zn-superoxide dismutase mutant mice. J Neurochem 96:1349–1361

    Article  PubMed  CAS  Google Scholar 

  • Darios F, Corti O, Lucking CB, Hampe C, Muriel MP, Abbas N, Gu WJ, Hirsch EC, Rooney T, Ruberg M, Brice A (2003) Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death. Hum Mol Genet 12:517–526

    Article  PubMed  CAS  Google Scholar 

  • Davidzon G, Greene P, Mancuso M, Klos KJ, Ahlskog JE, Hirano M, DiMauro S (2006) Early-onset familial parkinsonism due to POLG mutations. Ann Neurol 59:859–862

    Article  PubMed  CAS  Google Scholar 

  • Davies S, Ramsden DB (2001) Huntington’s disease. Mol Pathol 54:409–413

    PubMed  CAS  Google Scholar 

  • Dawson TM, Dawson VL (2003) Molecular pathways of neurodegeneration in Parkinson’s disease. Science 302:819–822

    Article  PubMed  CAS  Google Scholar 

  • De Benedictis G, Rose G, Carrieri G, De Luca M, Falcone E, Passarino G, Bonafè M, Monti D, Baggio G, Bertolini S, Mari D, Mattace R, Franceschi C (1999) Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans. FASEB J 13:1532–1536

    PubMed  Google Scholar 

  • De Coo IF, Renier WO, Ruitenbeek W, Ter Laak HJ, Bakker M, Schagger H, Van Oost BA, Smeets HJ (1999) A 4-base pair deletion in the mitochondrial cytochrome b gene associated with Parkinsonism/MELAS overlap syndrome. Ann Neurol 45:130–133

    Article  PubMed  Google Scholar 

  • Dhaliwal GK, Grewal RP (2000) Mitochondrial DNA deletion mutation levels are elevated in ALS brains. Neuroreport 11:2507–2509

    Article  PubMed  CAS  Google Scholar 

  • Drake J, Link CD, Butterfield DA (2003) Oxidative stress precedes fibrillar deposition of Alzheimer’s disease amyloid beta-peptide (1–42) in a transgenic Caenorhabditis elegans model. Neurobiol Aging 24:415–420

    Article  PubMed  CAS  Google Scholar 

  • Echaniz-Laguna A, Zoll J, Ponsot E, N’guessan B, Tranchant C, Loeffler JP, Lampert E (2006) Muscular mitochondrial function in amyotrophic lateral sclerosis is progressively altered as the disease develops: a temporal study in man. Exp Neurol 198:25–30

    Article  PubMed  CAS  Google Scholar 

  • Eckert A, Keil U, Marques CA, Bonert A, Frey C, Schussel K, Muller WE (2003) Mitochondrial dysfunction, apoptotic cell death, and Alzheimer’s disease. Biochem Pharmacol 66:1627–1634

    Article  PubMed  CAS  Google Scholar 

  • Elson JL, Herrnstadt C, Preston G, Thal L, Morris CM, Edwardson JA, Beal MF, Turnbull DM, Howell N (2006) Does the mitochondrial genome play a role in the etiology of Alzheimer’s disease? Hum Genet 119:241–254

    Article  PubMed  CAS  Google Scholar 

  • Estevez AG, Crow JP, Sampson JB, Reiter C, Zhuang Y, Richardson GJ, Tarpey MM, Barbetio L, Beckman JS (1999) Induction of nitric oxide-dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase. Science 286:2498–2500

    Article  PubMed  CAS  Google Scholar 

  • Ferri A, Cozzolino M, Crosio C, Nencini M, Casciati A, Gralla EB, Rotilio G, Valentine JS, Carri MT (2006) Familial ALS-superoxide dismutases associate with mitochondria and shift their redox potentials. Proc Natl Acad Sci USA 103:13860–13865

    Article  PubMed  CAS  Google Scholar 

  • Gabuzda D, Busciglio J, Chen LB, Matsudaira P, Yankner BA (1994) Inhibition of energy metabolism alters the processing of amyloid precursor protein and induces a potentially amyloidogenic derivative. J Biol Chem 269:13623–13628

    PubMed  CAS  Google Scholar 

  • Gajewski CD, Lin MT, Cudkowicz ME, Beal MF, Manfredi G (2003) Mitochondrial DNA from platelets of sporadic ALS patients restores normal respiratory functions in rho(0) cells, Exp Neurol 179:229–235

    Article  PubMed  CAS  Google Scholar 

  • Gardian G, Vecsei L (2004) Huntington’s disease: pathomechanism and therapeutic perspectives. J Neural Transm 111:1485–1494

    Article  PubMed  CAS  Google Scholar 

  • Ghezzi D, Marelli C, Achilli A, Goldwurm S, Pezzoli G, Barone P, Pellecchia MT, Stanzione P, Brusa L, Bentivoglio AR, Bonuccelli U, Petrozzi L, Abbruzzese G, Marchese R, Cortelli P, Grimaldi D, Martinelli P, Ferrarese C, Garavaglia B, Sangiorgi S, Carelli V, Torroni A, Albanese A, Zeviani M (2005) Mitochondrial DNA haplogroup K is associated with a lower risk of Parkinson’s disease in Italians. Eur J Hum Genet 13:748–752

    Article  PubMed  CAS  Google Scholar 

  • Giacchetti M, Monticelli A, De Biase I, Pianese L, Turano M, Filla A, De Michele G, Cocozza S (2004) Mitochondrial DNA haplogroups influence the Friedreich’s ataxia phenotype. J Med Genet 41:293–295

    Article  PubMed  CAS  Google Scholar 

  • Gibson GE, Haroutunian V, Zhang H, Park LC, Shi Q, Lesser M, Mohs RC, Sheu RK, Blass JP (2000) Mitochondrial damage in Alzheimer’s disease varies with apolipoprotein E genotype. Ann Neurol 48:297–303

    Article  PubMed  CAS  Google Scholar 

  • Goebel HH, Heipertz R, Scholz W, Iqbal K, Tellez-Nagel I (1978) Juvenile Huntington chorea: clinical, ultrastructural, and biochemical studies. Neurology 28:23–31

    PubMed  CAS  Google Scholar 

  • Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281:1309–1312

    Article  PubMed  CAS  Google Scholar 

  • Green DR, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305:626–629

    Article  PubMed  CAS  Google Scholar 

  • Gu M, Cooper JM, Taanman JW, Schapira AH (1998) Mitochondrial DNA transmission of the mitochondrial defect in Parkinson’s disease. Ann Neurol 44:177–186

    Article  PubMed  CAS  Google Scholar 

  • Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE, Watkins PC, Ottina K, Wallace MR, Sakaguchi AY, Young AB, Shoulson I, Bonilla E, Martin JB (1983) A polymorphic DNA marker genetically linked to Huntington’s disease. Nature 306:234–238

    Article  PubMed  CAS  Google Scholar 

  • Gusella JF, McDonald ME (1995) Huntington’s disease. Semin Cell Biol 6: 21–28

    Article  PubMed  CAS  Google Scholar 

  • Hansson CA, Frykman S, Farmery MR, Nilsberth C, Pursglove SE, Ito A, Winblad B, Cowburn RF, Thyberg J, Ankarcrona M (2004) Nicastrin, presenilin APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria. J Biol Chem 279:51654–51660

    Article  PubMed  CAS  Google Scholar 

  • Hattori N, Tanaka M, Ozawa T, Mizuno Y (1991) Immunohistochemical studies on complexes I, II, III, and IV of mitochondria in Parkinson’s disease. Ann Neurol 30:563–571

    Article  PubMed  CAS  Google Scholar 

  • Higgins CM, Jung C, Xu Z (2003) ALS-associated mutant SOD1G93A causes mitochondrial vacuolation by expansion of the intermembrane space and by involvement of SOD1 aggregation and peroxisomes. BMC Neurosci 4:16

    Article  PubMed  Google Scholar 

  • Hirano A, Donnenfeld H, Sasaki S, Nakano I (1984) Fine structural observations of neurofilamentous changes in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 43:461–470

    PubMed  CAS  Google Scholar 

  • Horvath R, Kley RA, Lochmuller H, Vorgerd M (2007) Parkinson syndrome, neuropathy, and myopathy caused by the mutation A8344G (MERRF) in tRNALys. Neurology 68:56–58

    Article  PubMed  Google Scholar 

  • Huerta C, Castro MG, Coto E, Blazquez M, Ribacoba R, Guisasola LM, Salvador C, Martinez C, Lahoz CH, Alvarez V (2005) Mitochondrial DNA polymorphisms and risk of Parkinson’s disease in Spanish population. J Neurol Sci 236:49–54

    Article  PubMed  CAS  Google Scholar 

  • Ito S, Ohta S, Nishimaki K, Kagawa Y, Soma R, Kuno SY, Komatsuzaki Y, Mizusawa H, Hayashi J (1999) Functional integrity of mitochondrial genomes in human platelets and autopsied brain tissues from elderly patients with Alzheimer’s disease. Proc Natl Acad Sci USA 96:2099–2103

    Article  PubMed  CAS  Google Scholar 

  • Jenkins BG, Koroshetz WJ, Beal MF, Rosen BR (1993) Evidence for impairment of energy metabolism in vivo in Huntington’s disease using localized 1H NMR spectroscopy. Neurology 43:2689–2695

    PubMed  CAS  Google Scholar 

  • Jung C, Higgins CM, Xu Z (2002) Mitochondrial electron transport chain complex dysfunction in a transgenic mouse model for amyotrophic lateral sclerosis. J Neurochem 83:535–545

    Article  PubMed  CAS  Google Scholar 

  • Khan SM, Cassarino DS, Abramova NN, Keeney PM, Borland MK, Trimmer PA, Krebs CT, Bennett JC, Parks JK, Swerdlow RH, Parker WD Jr, Bennett JP Jr (2000) Alzheimer’s disease cybrids replicate beta-amyloid abnormalities through cell death pathways. Ann Neurol 48:148–155

    Article  PubMed  CAS  Google Scholar 

  • Kim RH, Peters M, Jang Y, Shi W, Pintilie M, Fletcher GC, DeLuca C, Liepa J, Zhou L, Snow B, Binari RC, Manoukian AS, Bray MR, Liu FF, Tsao MS, Mak TW (2005) DJ-1, a novel regulator of the tumor suppressor PTEN. Cancer Cell 7:263–273

    Article  PubMed  CAS  Google Scholar 

  • King MP, Attardi G (1989) Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science 246:500–503

    Article  PubMed  CAS  Google Scholar 

  • Kirkinezos IG, Bacman SR, Hernandez D, Oca-Cossio J, Arias LJ, Perez-Pinzon MA, Bradley WG, Moraes CT (2005) Cytochrome c association with the inner mitochondrial membrane is impaired in the CNS of G93A-SOD1 mice. J Neurosci 25:164–172

    Article  PubMed  CAS  Google Scholar 

  • Kish SJ, Bergeron C, Rajput A, Dozic S, Mastrogiacomo F, Chang LJ, Wilson JM, DiStefano LM, Nobrega JN (1992) Brain cytochrome oxidase in Alzheimer’s disease. J Neurochem 59:776–779

    Article  PubMed  CAS  Google Scholar 

  • Kong J, Xu Z (1998) Massive mitochondrial degeneration in motor neurons triggers the onset of amyotrophic lateral sclerosis in mice expressing a mutant SOD1. J Neurosci 18:3241–3250

    PubMed  CAS  Google Scholar 

  • Koroshetz WJ, Jenkins BG, Rosen BR, Beal MF (1997) Energy metabolism defects in Huntington’s disease and effects of coenzyme Q10. Ann Neurol 41:160–165

    Article  PubMed  CAS  Google Scholar 

  • Kraytsberg Y, Kudryavtseva E, McKee AC, Geula C, Kowall NW, Khrapko K (2006) Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nat Genet 38:518–520

    Article  PubMed  CAS  Google Scholar 

  • Kuroda Y, Mitsui T, Kunishige M, Matsumoto T (2006) Parkin enhances mitochondrial biogenesis in proliferating cells. Hum Mol Genet 15:883–895

    Article  PubMed  CAS  Google Scholar 

  • Langston JW, Forno LS, Tetrud J, Reeves AG, Kaplan JA, Karluk D (1999) Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann Neurol 46:598–605

    Article  PubMed  CAS  Google Scholar 

  • Li SH, Cheng AL, Zhou H, Lam S, Rao M, Li H, Li XJ (2002) Interaction of Huntington disease protein with transcriptional activator Sp1. Mol Cell Biol 22:1277–1287

    Article  PubMed  CAS  Google Scholar 

  • Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Lillo C, Jonsson PA, Van de Velde C, Ward CM, Miller TM, Subramaniam JR, Rothstein JD, Marklund S, Andersen PM, Brannstrom T, Gredal O, Wong PC, Williams DS, Cleveland DW (2004) Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria. Neuron 43:5–17

    Article  PubMed  CAS  Google Scholar 

  • Luoma P, Melberg A, Rinne JO, Kaukonen JA, Nupponen NN, Chalmers RM, Oldfors A, Rautakorpi I, Peltonen L, Majamaa K, Somer H, Suomalainen A (2004) Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study. Lancet 364:875–882

    Article  PubMed  CAS  Google Scholar 

  • Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, Caspersen C, Chen X, Pollak S, Chaney M, Trinchese F, Liu S, Gunn-Moore F, Lue LF, Walker DG, Kuppusamy P, Zewier ZL, Arancio O, Stern D, Yan SS, Wu H (2004) ABAD directly links Abeta to mitochondrial toxicity in Alzheimer’s disease. Science 304:448–452

    Article  PubMed  CAS  Google Scholar 

  • Maguire-Zeiss KA, Federoff HJ (2003) Convergent pathobiologic model of Parkinson’s disease. Ann NY Acad Sci 991:152–166

    Article  PubMed  CAS  Google Scholar 

  • Mancuso M, Filosto M, Bosetti F, Ceravolo R, Rocchi A, Tognoni G, Manca ML, Solaini G, Siciliano G, Murri L (2003) Decreased platelet cytochrome c oxidase activity is accompanied by increased blood lactate concentration during exercise in patients with Alzheimer disease. Exp Neurol 182:421–426

    Article  PubMed  CAS  Google Scholar 

  • Mancuso M, Conforti FL, Rocchi A, Tessitore A, Muglia M, Tedeschi G, Panza D, Monsurrò MR, Sola P, Mandrioli J, Choub A, DelCorona A, Manca ML, Mazzei R, Sprovieri T, Filosto M, Salviati A, Valentino P, Bono F, Caracciolo M, Simone IL, La Bella V, Majorana G, Siciliano G, Murri L, Quattrone A (2004a) Could mitochondrial haplogroups play a role in sporadic amyotrophic lateral sclerosis? Neurosci Lett 371:158–162

    Article  PubMed  CAS  Google Scholar 

  • Mancuso M, Filosto M, Oh SJ, DiMauro S (2004b) A novel POLG mutation in a family with ophtalmoplegia, neuropathy, and parkinsonism. Arch Neurol 61:1777–1779

    Article  PubMed  Google Scholar 

  • Mancuso M, Siciliano G, Filosto M, Murri L (2006) Mitochondrial dysfunction and Alzheimer’s disease: new developments. J Alz Dis 9:111–117

    Google Scholar 

  • Manfredi G, Xu Z (2005) Mitochondrial dysfunction and its role in motor neuron degeneration in ALS. Mitochondrion 5:77–87

    Article  PubMed  CAS  Google Scholar 

  • Mann VM, Cooper JM, Javoid-Agid F, Agid Y, Jennert P, Schapira AH (1990) Mitochondrial function and parental sex effect in Huntington’s disease. Lancet 336(8717):749

    Article  PubMed  CAS  Google Scholar 

  • Mann VM, Cooper JM, Krige D, Daniel SE, Schapira AH, Marsden CD (1992) Brain, skeletal muscle and platelet homogenate mitochondrial function in Parkinson’s disease. Brain 115:333–342

    Article  PubMed  Google Scholar 

  • Maurer I, Zierz S, Moller HJ (2000) A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients. Neurobiol Aging 21:455–462

    Article  PubMed  CAS  Google Scholar 

  • Mattiazzi M, D’Aurelio M, Gajewski CD, Martushova K, Kiaei M, Beal MF, Manfredi G (2002) Mutated human SOD1 causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice. J Biol Chem 277:29626–29633

    Article  PubMed  CAS  Google Scholar 

  • Migliore L, Fontana I, Trippi F, Colognato R, Coppedè F, Tognoni G, Nucciarone B, Siciliano G (2005a) Oxidative DNA damage in peripheral leukocytes of mild cognitive impairment and AD patients. Neurobiol Aging 26:567–573

    Article  PubMed  CAS  Google Scholar 

  • Migliore L, Fontana I, Colognato R, Coppedè F, Siciliano G, Murri L (2005b) Searching for the role and the most suitable biomarkers of oxidative stress in Alzheimer’s disease and in other neurodegenerative diseases. Neurobiol Aging 26:587–595

    Article  PubMed  CAS  Google Scholar 

  • Mutisya EM, Bowling AC, Beal MF (1994) Cortical cytochrome oxidase activity is reduced in Alzheimer’s disease. J Neurochem 63:2179–2184

    Article  PubMed  CAS  Google Scholar 

  • Niemi AK, Hervonen A, Hurme M, Karhunen PJ, Jylha M, Majamaa K (2003) Mitochondrial DNA polymorphisms associated with longevity in a Finnish population. Hum Genet 112:29–33

    Article  PubMed  CAS  Google Scholar 

  • Nunomura A, Honda K, Takeda A, Hirai K, Zhu X, Smith MA, Perry G (2006) Oxidative Damage to RNA in Neurodegenerative Diseases. J Biomed Biotechnol 2006:82323

    PubMed  Google Scholar 

  • Ohyagi Y, Yamada T, Nishioka K, Clarke NJ, Tomlinson AJ, Naylor S, Nakabeppu Y, Kira J, Younkin SG (2000) Selective increase in cellular A beta 42 is related to apoptosis but not necrosis. Neuroreport 11:167–171

    Article  PubMed  CAS  Google Scholar 

  • Ojaimi J, Masters CL, McLean C, Opeskin K, McKelvie P, Byrne E (1999) Irregular distribution of cytochrome c oxidase protein subunits in aging and Alzheimer’s disease. Ann Neurol 46:656–660

    Article  PubMed  CAS  Google Scholar 

  • Onyango IG, Bennett JP Jr, Tuttle JB (2005) Endogenous oxidative stress in sporadic Alzheimer’s disease neuronal cybrids reduces viability by increasing apoptosis through pro-death signaling pathways and is mimicked by oxidant exposure of control cybrids. Neurobiol Dis 19:312–322

    Article  PubMed  CAS  Google Scholar 

  • Parker WD, Boyson SJ, Luder AS, Parks JK (1990a) Evidence for a defect in NADH: ubiquinone oxidoreductase (complex I) in Huntington’s disease. Neurology 40:1231–1234

    PubMed  Google Scholar 

  • Parker WD Jr, Filley CM, Parks JK (1990b) Cytochrome oxidase deficiency in Alzheimer’s disease. Neurology 40:1302–1303

    PubMed  Google Scholar 

  • Pasinelli P, Belford ME, Lennon N, Bacskai BJ, Hyman BT, Trotti D, Brown RH Jr (2004) Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria. Neuron 43:19–30

    Article  PubMed  CAS  Google Scholar 

  • Perry G, Nunomura A, Hirai K, Zhu X, Perez M, Avila J, Castellani RJ, Atwood CS, Aliev G, Sayre LM, Takeda A, Smith MA (2002) Is oxidative damage the fundamental pathogenic mechanism of Alzheimer’s and other neurodegenerative diseases? Free Radic Biol Med 33:1475–1479

    Article  PubMed  CAS  Google Scholar 

  • Petit A, Kawarai T, Paitel E, Sanjo N, Maj M, Scheid M, Chen F, Gu Y, Hasegawa H, Salehi-Rad S, Wang L, Rogaeva E, Fraser P, Robinson B, St George-Hyslop P, Tandon A (2005) Wild-type PINK1 prevents basal and induced neuronal apoptosis, a protective effect abrogated by Parkinson disease-related mutations. J Biol Chem 280:34025–34032

    Article  PubMed  CAS  Google Scholar 

  • Praticò D, Delanty N (2000) Oxidative injury in diseases of the central nervous system: focus on Alzheimer’s disease. Am J Med 109:577–585

    Article  PubMed  Google Scholar 

  • Pyle A, Foltynie T, Tiangyou W, Foltynie T, Tiangyou W, Lambert C, Keers SM, Allcock LM, Davison J, Lewis SJ, Perry RH, Barker R, Burn DJ, Chinnery PF (2005) Mitochondrial DNA haplogroup cluster UKJT reduces the risk of PD. Ann Neurol 57:564–567

    Article  PubMed  Google Scholar 

  • Reddy PH, Beal MF (2005) Are mitochondria critical in the pathogenesis of Alzheimer’s disease? Brain Res Rev 49(3):618–632

    Article  PubMed  CAS  Google Scholar 

  • Rego AC, Oliveira CR (2003) Mitochondrial dysfunction and reactive oxygen species in excitotoxicity and apoptosis: implications for the pathogenesis of neurodegenerative diseases. Neurochem Res 28:1563–1574

    Article  PubMed  CAS  Google Scholar 

  • Reynier P, Penisson-Besnier I, Moreau C, Savagner F, Vielle B, Emile J, Dubas F, Malthiery Y (1999) mtDNA haplogroup J: a contributing factor of optic neuritis. Eur J Hum Genet 7:404–406

    Article  PubMed  CAS  Google Scholar 

  • Ro LS, Lai SL, Chen CM, Chen ST (2003) Deleted 4977-bp mitochondrial DNA mutation is associated with sporadic amyotrophic lateral sclerosis: a hospital-based case-control study. Muscle Nerve 28:737–743

    Article  PubMed  CAS  Google Scholar 

  • Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O’Regan JP, Deng HX, Rahmani Z, Krizus A, McKenna-Yasek D, Cayabyab A, Gaston SM, Berger R, Tanzi RE, Halperin JJ, Herzfeldt B, Van den Bergh R, Hung W, Bird T, Deng G, Mulder DW, Smyth C, Laing NG, Soriano E, Pericak-Vance MA, Haines J, Rouleau GA, Gusella JS, Horvitz HR, Brown RH Jr (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62

    Article  PubMed  CAS  Google Scholar 

  • Ross OA, McCormack R, Curran MD, Duguid RA, Barnett YA, Rea IM, Middleton D (2001) Mitochondrial DNA polymorphism: its role in longevity of the Irish population. Exp Gerontol 36:1161–1178

    Article  PubMed  CAS  Google Scholar 

  • Santoro A, Salvioli S, Raule N, Capri M, Sevini F, Valensin S, Monti D, Bellizzi D, Passarino G, Rose G, De Benedictis G, Franceschi C (2006) Mitochondrial DNA involvement in human longevity. Biochim Biophys Acta 1757:1388–1399

    Article  PubMed  CAS  Google Scholar 

  • Sasaki S, Iwata M (1996) Impairment of fast axonal transport in the proximal axons of anterior horn neurons in amyotrophic lateral sclerosis. Neurology 47:535–540

    PubMed  CAS  Google Scholar 

  • Schapira AH, Mann VM, Cooper JM, Dexter D, Daniel SE, Jenner P, Clark JB, Marsden CD (1990) Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson’s disease. J Neurochem 55:2142–2145

    Article  PubMed  CAS  Google Scholar 

  • Schapira AH (1994) Evidence for mitochondrial dysfunction in Parkinson’s disease – a critical appraisal. Mov Disord 9:125–138

    Article  PubMed  CAS  Google Scholar 

  • Schapira AH (2006) Etiology of Parkinson’s disease. Neurology 66:S10–S23

    PubMed  Google Scholar 

  • Selkoe DJ (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev 81:741–766

    PubMed  CAS  Google Scholar 

  • Siciliano G, Mancuso M, Ceravolo R, Lombardi V, Iudice A, Bonuccelli U (2001) Mitochondrial DNA rearrangements in young onset parkinsonism: two case reports. J Neurol Neurosurg Psychiat 71:685–687

    Article  PubMed  CAS  Google Scholar 

  • Silvestri L, Caputo V, Bellacchio E, Atorino L, Dallapiccola B, Valente EM, Casari G. (2005) Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum Mol Genet 14:3477–3492

    Article  PubMed  CAS  Google Scholar 

  • Simonian SA, Hyman BT (1994) Functional alterations in Alzheimer’s disease: selective loss of mitochondrial-encoded cytochrome oxidase mRNA in the hippocampal formation. J Neuropathol Exp Neurol 53:508–512

    PubMed  CAS  Google Scholar 

  • Small GW, Mazziotta JC, Collins MT, Baxter LR, Phelps ME, Mandelkern MA, Kaplan A, La Rue A, Adamson CF, Chang L (1995) Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA 273:942–947

    Article  PubMed  CAS  Google Scholar 

  • Song DD, Shults CW, Sisk A, Rockenstein E, Masliah E (2004) Enhanced substantia nigra mitochondrial pathology in human α-synuclein transgenic mice after treatment with MPTP. Exp Neurol 186:158–172

    Article  PubMed  CAS  Google Scholar 

  • Sorbi S, Bird ED, Blass JP (1983) Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Ann Neurol 13:72–78

    Article  PubMed  CAS  Google Scholar 

  • Stavrovskaya IG, Kristal BS (2005) The powerhouse takes control of the cell: is the mitochondrial permeability transition a viable therapeutic target against neuronal dysfunction and death? Free Radic Biol Med 38:687–697

    Article  PubMed  CAS  Google Scholar 

  • Strauss KM, Martins LM, Plun-Favreau H, Marx FP, Kautzmann S, Berg D, Gasser T, Wszolek Z, Muller T, Bornemann A, Wolburg H, Downward J, Riess O, Schulz JB, Kruger R (2005) Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson’s disease. Hum Mol Genet 14:2099–2111

    Article  PubMed  CAS  Google Scholar 

  • Suzuki Y, Imai Y, Nakayama H, Takahashi K, Takio K, Takahashi R (2001) A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol Cell 8:613–621

    Article  PubMed  CAS  Google Scholar 

  • Swerdlow RH, Parks JK, Cassarino DS, Maguire DJ, Maguire RS, Bennett JP Jr, Davis RE, Parker WD Jr (1997) Cybrids in Alzheimer’s disease: a cellular model of the disease? Neurology 49:918–925

    PubMed  CAS  Google Scholar 

  • Swerdlow RH, Parks JK, Cassarino DS, Trimmer PA, Miller SW, Maguire DJ, Sheehan JP, Maguire RS, Pattee G, Juel VC, Phillips LH, Tuttle JB, Bennett JP Jr, Davis RE, Parker WD Jr (1998) Mitochondria in sporadic amyotrophic lateral sclerosis. Exp Neurol 153:135–142

    Article  PubMed  CAS  Google Scholar 

  • Takeuchi H, Kobayashi Y, Ishigaki S, Doyu M, Sobue G (2002) Mitochondrial localization of mutant superoxide dismutase 1 triggers caspase-dependent cell death in a cellular model of familial amyotrophic lateral sclerosis. J Biol Chem 277:50966–50972

    Article  PubMed  CAS  Google Scholar 

  • Tanaka M, Gong JS, Zhang J, Yoneda M, Yagi K (1998) Mitochondrial genotype associated with longevity. Lancet 351:185–186

    Article  PubMed  CAS  Google Scholar 

  • Thiffault C, Bennett JP Jr (2005) Cyclical mitochondrial deltapsiM fluctuations linked to electron transport, F0F1 ATP-synthase and mitochondrial Na+/Ca+2 exchange are reduced in Alzheimer’s disease cybrids. Mitochondrion 5:109–119

    Article  PubMed  CAS  Google Scholar 

  • Thyagarajan D, Bressman S, Bruno C, Przedborski S, Shanske S, Lynch T, Fahn S, DiMauro S (2000) A novel mitochondrial 12S rRNA point mutation in Parkinsonism, deafness and neuropathy. Ann Neurol 48:730–736

    Article  PubMed  CAS  Google Scholar 

  • Tiangyou W, Hudson G, Ghezzi D, Ferrari G, Zeviani M, Burn DJ, Chinnery PF (2006) POLG1 in idiopathic Parkinson disease. Neurology 67:1698–1700

    Article  PubMed  CAS  Google Scholar 

  • Torroni A, Petrozzi M, D’Urbano L, Sellitto D, Zeviani M, Carrara F, Carducci C, Leuzzi V, Carelli V, Barboni P, De Negri A, Scozzari R (1997) Haplotype and phylogenetic analyses suggest that one European-specific mtDNA background plays a role in the expression of Leber hereditary optic neuropathy by increasing the penetrance of the primary mutations 11778 and 14484. Am J Hum Genet 60:1107–1121

    PubMed  CAS  Google Scholar 

  • Trimmer PA, Keeney PM, Borland MK, Simon FA, Almeida J, Swerdlow RH, Parks JP, Parker WD Jr, Bennett JP Jr (2004) Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer’s disease worsen with passage in culture. Neurobiol Dis 15:29–39

    Article  PubMed  CAS  Google Scholar 

  • Trimmer PA, Borland MK (2005) Differentiated Alzheimer’s disease transmitochondrial cybrid cell lines exhibit reduced organelle movement. Antioxid Redox Signal 7:1101–1109

    Article  PubMed  CAS  Google Scholar 

  • van der Walt JM, Nicodemus KK, Martin ER, Scott WK, Nance MA, Watts RL, Hubble JP, Haines JL, Koller WC, Lyons K, Pahwa R, Stern MB, Colcher A, Hiner BC, Jankovic J, Ondo WG, Allen FH Jr, Goetz CG, Small GW, Mastaglia F, Stajich JM, McLaurin AC, Middleton LT, Scott BL, Schmechel DE, Pericak-Vance MA, Vance JM (2003) Mitochondrial polymorphisms significantly reduce the risk of Parkinson’s disease. Am J Hum Genet 72:804–811

    Article  PubMed  Google Scholar 

  • van der Walt JM, Dementieva YA, Martin ER, Scott WK, Nicodemus KK, Kroner CC, Welsh-Bohmer KA, Saunders AM, Roses AD, Small GW, Schmechel DE, Murali Doraiswamy P, Gilbert JR, Haines JL, Vance JM, Pericak-Vance MA (2004) Analysis of European mitochondrial haplogroups with Alzheimer disease risk. Neurosci Lett 365:28–32

    Article  PubMed  CAS  Google Scholar 

  • Vielhaber S, Kunz D, Winkler K, Wiedemann FR, Kirches E, Feistner H, Heinze HJ, Elger CE, Schubert W, Kunz WS (2000) Mitochondrial DNA abnormalities in skeletal muscle of patients with sporadic amyotrophic lateral sclerosis. Brain 123:1339–1348

    Article  PubMed  Google Scholar 

  • Vijayvergiya C, Beal MF, Buck J, Manfredi G (2005) Mutant superoxide dismutase 1 forms aggregates in the brain mitochondrial matrix of amyotrophic lateral sclerosis mice. J Neurosci 25:2463–2470

    Article  PubMed  CAS  Google Scholar 

  • Wallace DC (2005) A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 39:359–407

    Article  PubMed  CAS  Google Scholar 

  • West AB, Moore DJ, Biskup S, Bugayenko A, Smith WW, Ross CA, Dawson VL, Dawson TM (2005) Parkinson’s disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci USA 102:16842–16847

    Article  PubMed  CAS  Google Scholar 

  • Wiedemann FR, Winkler K, Kuznetsov AV, Bartels C, Vielhaber S, Feistner H, Kunz WS (1998) Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis. J Neurol Sci 156:65–72

    Article  PubMed  CAS  Google Scholar 

  • Wiedemann FR, Manfredi G, Mawrin C, Beal MF, Schon EA (2002) Mitochondrial DNA and respiratory chain function in spinal cords of ALS patients. J Neurochem 80:616–625

    Article  PubMed  CAS  Google Scholar 

  • Wong PC, Pardo CA, Borchelt DR, Lee MK, Copeland NG, Jenkins NA, Sisodia SS, Cleveland DW, Price DL (1995) An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron 14:1105–1116

    Article  PubMed  CAS  Google Scholar 

  • Wong-Riley M, Antuono P, Ho KC, Egan R, Hevner R, Liebl W, Huang Z, Rachel R, Jones J (1997) Cytochrome oxidase in Alzheimer’s disease: biochemical, histochemical, and immunohistochemical analyses of the visual and other systems. Vision Res 37:3593–3608

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuroscience, University of Pisa, Via Roma 67, Pisa, 56126, Italy

    Lucia Petrozzi, Giulia Ricci, Noemi J. Giglioli, Gabriele Siciliano & Michelangelo Mancuso

Authors
  1. Lucia Petrozzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giulia Ricci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Noemi J. Giglioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gabriele Siciliano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michelangelo Mancuso
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michelangelo Mancuso.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Petrozzi, L., Ricci, G., Giglioli, N.J. et al. Mitochondria and Neurodegeneration. Biosci Rep 27, 87–104 (2007). https://doi.org/10.1007/s10540-007-9038-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10540-007-9038-z

Keywords

Search

Navigation