Mice lacking alpha-synuclein are resistant to mitochondrial toxins

被引：166
作者：
Klivenyi, P
Siwek, D
Gardian, G
Yang, LH
Starkov, A
Cleren, C
Ferrante, RJ
Kowall, NW
Abellovich, A
Beal, MF
机构：
[1] Cornell Univ, Dept Neurol & Neurosci, Weill Med Coll, New York Presbyterian Hosp, New York, NY 10021 USA
[2] Bedford VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bedford, MA USA
[3] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA
[4] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA
[5] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA
[6] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York Presbyterian Hosp, New York, NY 10021 USA
来源：
NEUROBIOLOGY OF DISEASE | 2006年 / 21卷 / 03期
关键词：
MPTP; paraquat; 3-nitropropionic acid; malonate; MPP+; MPP+ levels; vesicular uptake; DHBA;
D O I：
10.1016/j.nbd.2005.08.018
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
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. (C) 2005 Elsevier Inc. All rights reserved.
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收藏
页码：541 / 548
页数：8
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