Benomyl, Aldehyde Dehydrogenase, DOPAL, and the Catecholaldehyde Hypothesis for the Pathogenesis of Parkinson's Disease

被引：49

作者：

Casida, John E. ^{[1
]}

Ford, Breanna ^{[1
]}

Jinsmaa, Yunden ^{[2
]}

Sullivan, Patti ^{[2
]}

Cooney, Adele ^{[2
]}

Goldstein, David S. ^{[2
]}

机构：

[1] Univ Calif Berkeley, Environm Chem & Toxicol Lab, Berkeley, CA 94720 USA

[2] NINDS, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res, Bethesda, MD 20892 USA

来源：

CHEMICAL RESEARCH IN TOXICOLOGY | 2014年 / 27卷 / 08期

关键词：

TOXIC DOPAMINE METABOLITE; OXIDATIVE STRESS; 3,4-DIHYDROXYPHENYLACETALDEHYDE; MECHANISM; INHIBITION; CATECHOLS;

D O I：

10.1021/tx5002223

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

The dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is detoxified mainly by aldehyde dehydrogenase (ALDH). We find that the fungicide benomyl potently and rapidly inhibits ALDH and builds up DOPAL in vivo in mouse striatum and in vitro in PC12 cells and human cultured fibroblasts and glial cells. The in vivo results resemble those noted previously with knockouts of the genes encoding ALDH1A1 and 2, a mouse model of aging-related Parkinson's disease (PD). Exposure to pesticides that inhibit ALDH may therefore increase PD risk via DOPAL buildup. This study lends support to the "catecholaldehyde hypothesis" that the autotoxic dopamine metabolite DOPAL plays a pathogenic role in PD.

引用

页码：1359 / 1361

页数：3

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