MPTP公司
髓过氧化物酶
神经毒素
神经退行性变
多巴胺能
多巴胺
中脑
化学
帕金森病
神经保护
药理学
神经科学
炎症
生物
免疫学
医学
生物化学
内科学
疾病
中枢神经系统
作者
Dong‐Kug Choi,Subramaniam Pennathur,Céline Perier,Kim Tieu,Peter Teismann,Du Chu Wu,Vernice Jackson‐Lewis,Miquel Vila,Jean Paul Vonsattel,Jay W. Heinecke,Serge Przedborski
标识
DOI:10.1523/jneurosci.0970-05.2005
摘要
Parkinson's disease (PD) is characterized by a loss of ventral midbrain dopaminergic neurons, which can be modeled by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Inflammatory oxidants have emerged as key contributors to PD- and MPTP-related neurodegeneration. Here, we show that myeloperoxidase (MPO), a key oxidant-producing enzyme during inflammation, is upregulated in the ventral midbrain of human PD and MPTP mice. We also show that ventral midbrain dopaminergic neurons of mutant mice deficient in MPO are more resistant to MPTP-induced cytotoxicity than their wild-type littermates. Supporting the oxidative damaging role of MPO in this PD model are the demonstrations that MPO-specific biomarkers 3-chlorotyrosine and hypochlorous acid-modified proteins increase in the brains of MPTP-injected mice. This study demonstrates that MPO participates in the MPTP neurotoxic process and suggests that inhibitors of MPO may provide a protective benefit in PD.
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