Benomyl, aldehyde dehydrogenase, DOPAL, and the catecholaldehyde hypothesis for the pathogenesis of Parkinson's disease.

Abstract:

: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.

journal_name

Chem Res Toxicol

authors

Casida JE,Ford B,Jinsmaa Y,Sullivan P,Cooney A,Goldstein DS

doi

10.1021/tx5002223

subject

Has Abstract

pub_date

2014-08-18 00:00:00

pages

1359-61

issue

8

eissn

0893-228X

issn

1520-5010

journal_volume

27

pub_type

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