David S. Goldstein, Patti Sullivan, Adele Cooney, Yunden Jinsmaa, Rachel Sullivan, Daniel J. Gross, Courtney Holmes, Irwin J. Kopin and Yehonatan Sharabi Vesicular uptake blockade generates the toxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde in PC12 cells: relevance to the pathogenesis of Parkinson's disease Journal of Neurochemistry 123
Death by Suicide: Catecholamine Autotoxicity Mediated by DOPAL
Dopamine metabolism is channeled through the toxic catecholaldehyde, 3,4-dihydroxyphenylaldehyde (DOPAL), via monoamine oxidase acting on cytosolic dopamine. We report that blockade of the vesicular monoamine transporter or inhibition of aldehyde/aldose reductase and aldehyde dehydrogenase augment DOPAL generation. In catecholaminergic cells, DOPAL contributes to apoptosis and alpha-synuclein oligomerization. The results fit with the ‘catecholaldehyde hypothesis’ for the pathogenesis of Parkinson disease.
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