title: 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.
authors.affiliation: Environmental Chemistry and Toxicology Laboratory, University of California , Berkeley, California 94720-3112, United States.
authors.forename: John E
authors.initials: JE
authors.lastname: Casida
authors.forename: Breanna
authors.initials: B
authors.lastname: Ford
authors.forename: Yunden
authors.initials: Y
authors.lastname: Jinsmaa
authors.forename: Patti
authors.initials: P
authors.lastname: Sullivan
authors.forename: Adele
authors.initials: A
authors.lastname: Cooney
authors.forename: David S
authors.initials: DS
authors.lastname: Goldstein
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000447:Aldehydes / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D001542:Benomyl / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D016716:PC12 Cells; D010300:Parkinson Disease / Q000209:etiology*; D051381:Rats
chemical_list: D000447:Aldehydes; D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; C007430:3,4-dihydroxyphenylacetaldehyde; D000444:Aldehyde Dehydrogenase; C027576:4-hydroxy-2-nonenal; D001542:Benomyl