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

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• 作者：John E. Casida ; Breanna Ford ; Yunden Jinsmaa ; Patti Sullivan ; Adele Cooney ; David S. Goldstein
• 刊名：Chemical Research in Toxicology
• 出版年：2014
• 出版时间：August 18, 2014
• 年：2014
• 卷：27
• 期：8
• 页码：1359-1361
• 全文大小：233K
• ISSN：1520-5010

文摘

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鈥檚 disease (PD). Exposure to pesticides that inhibit ALDH may therefore increase PD risk via DOPAL buildup. This study lends support to the 鈥渃atecholaldehyde hypothesis鈥?that the autotoxic dopamine metabolite DOPAL plays a pathogenic role in PD.