Mice lacking alpha-synuclein are resistant to mitochondrial toxins

P. Klivényi, Donald Siwek, Gabrielle Gardian, Lichuan Yang, Anatoly Starkov, Carine Cleren, Robert J. Ferrante, Neil W. Kowall, Asa Abeliovich, M. Flint Beal

Research output: Contribution to journalArticle

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Abstract

Abnormalities in the function of α-synuclein are implicated in the pathogenesis of Parkinson's disease (PD). We found that α-synuclein- deficient mice are resistant to MPTP-induced degeneration of dopaminergic neurons. There was dose-dependent protection against loss of both dopamine in the striatum and dopamine transporter (DAT) immunoreactive neurons in the substantia nigra. These effects were not due to alterations in MPTP processing. We found that α-synuclein-deficient mice are also resistant to both malonate and 3-nitropropionic acid (3-NP) neurotoxicity. There was reduced generation of reactive oxygen species in α-synuclein-deficient mice following administration of 3-NP. These findings implicate α-synuclein as a modulator of oxidative damage, which has been implicated in neuronal death produced by MPTP and other mitochondrial toxins.

Original languageEnglish
Pages (from-to)541-548
Number of pages8
JournalNeurobiology of Disease
Volume21
Issue number3
DOIs
Publication statusPublished - Mar 2006

Fingerprint

Synucleins
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Dopamine Plasma Membrane Transport Proteins
Dopaminergic Neurons
Substantia Nigra
Parkinson Disease
Reactive Oxygen Species
Dopamine
Mouse Snca protein
Neurons

Keywords

  • 3-Nitropropionic acid
  • DHBA
  • Malonate
  • MPP levels
  • MPP
  • MPTP
  • Paraquat
  • Vesicular uptake

ASJC Scopus subject areas

  • Neurology

Cite this

Klivényi, P., Siwek, D., Gardian, G., Yang, L., Starkov, A., Cleren, C., ... Beal, M. F. (2006). Mice lacking alpha-synuclein are resistant to mitochondrial toxins. Neurobiology of Disease, 21(3), 541-548. https://doi.org/10.1016/j.nbd.2005.08.018

Mice lacking alpha-synuclein are resistant to mitochondrial toxins. / Klivényi, P.; Siwek, Donald; Gardian, Gabrielle; Yang, Lichuan; Starkov, Anatoly; Cleren, Carine; Ferrante, Robert J.; Kowall, Neil W.; Abeliovich, Asa; Beal, M. Flint.

In: Neurobiology of Disease, Vol. 21, No. 3, 03.2006, p. 541-548.

Research output: Contribution to journalArticle

Klivényi, P, Siwek, D, Gardian, G, Yang, L, Starkov, A, Cleren, C, Ferrante, RJ, Kowall, NW, Abeliovich, A & Beal, MF 2006, 'Mice lacking alpha-synuclein are resistant to mitochondrial toxins', Neurobiology of Disease, vol. 21, no. 3, pp. 541-548. https://doi.org/10.1016/j.nbd.2005.08.018
Klivényi, P. ; Siwek, Donald ; Gardian, Gabrielle ; Yang, Lichuan ; Starkov, Anatoly ; Cleren, Carine ; Ferrante, Robert J. ; Kowall, Neil W. ; Abeliovich, Asa ; Beal, M. Flint. / Mice lacking alpha-synuclein are resistant to mitochondrial toxins. In: Neurobiology of Disease. 2006 ; Vol. 21, No. 3. pp. 541-548.
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