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PMID:16298531

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Citation

Klivenyi, P, Siwek, D, Gardian, G, Yang, L, Starkov, A, Cleren, C, Ferrante, RJ, Kowall, NW, Abeliovich, A and Beal, MF (2006) Mice lacking alpha-synuclein are resistant to mitochondrial toxins. Neurobiol. Dis. 21:541-8

Abstract

Abnormalities in the function of alpha-synuclein are implicated in the pathogenesis of Parkinson's disease (PD). We found that alpha-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 alpha-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 alpha-synuclein-deficient mice following administration of 3-NP. These findings implicate alpha-synuclein as a modulator of oxidative damage, which has been implicated in neuronal death produced by MPTP and other mitochondrial toxins.

Links

PubMed Online version:10.1016/j.nbd.2005.08.018

Keywords

Animals; Malonates/toxicity; Mice; Mice, Mutant Strains; Mitochondria/drug effects; Neurons/drug effects; Neurons/pathology; Neurotoxins/pharmacology; Nitro Compounds/toxicity; Parkinsonian Disorders/pathology; Parkinsonian Disorders/physiopathology; Propionic Acids/toxicity; alpha-Synuclein/deficiency; alpha-Synuclein/genetics

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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References

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