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 Toxicoljournal_title
Chemical research in toxicologyauthors
Casida JE,Ford B,Jinsmaa Y,Sullivan P,Cooney A,Goldstein DSdoi
10.1021/tx5002223subject
Has Abstractpub_date
2014-08-18 00:00:00pages
1359-61issue
8eissn
0893-228Xissn
1520-5010journal_volume
27pub_type
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