title: Mice lacking alpha-synuclein are resistant to mitochondrial toxins.
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.
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, 525 East 68th Street, New York, NY 10021, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Klivenyi
authors.forename: Donald
authors.initials: D
authors.lastname: Siwek
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Gardian
authors.forename: Lichuan
authors.initials: L
authors.lastname: Yang
authors.forename: Anatoly
authors.initials: A
authors.lastname: Starkov
authors.forename: Carine
authors.initials: C
authors.lastname: Cleren
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ferrante
authors.forename: Neil W
authors.initials: NW
authors.lastname: Kowall
authors.forename: Asa
authors.initials: A
authors.lastname: Abeliovich
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
mesh_terms: D000818:Animals; D008314:Malonates / Q000633:toxicity; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology*; D009574:Nitro Compounds / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology*; D011422:Propionates / Q000633:toxicity; D051844:alpha-Synuclein / Q000172:deficiency* / Q000235:genetics
chemical_list: D008314:Malonates; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D051844:alpha-Synuclein; C030290:malonic acid; C015392:3-nitropropionic acid