Dopamine-derived biological reactive intermediates and protein modifications: Implications for Parkinson's disease.

Dopamine (DA) undergoes monoamine oxidase catalyzed oxidative deamination to 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is metabolized primarily to 3,4-dihydroxyphenylacetic acid (DOPAC) via aldehyde dehydrogenase (ALDH). Previous studies demonstrated DOPAL to be neurotoxic, more so than DA and other metabolites, and implicated the aldehyde intermediate as a factor in the pathogenesis of Parkinson's disease (PD). However, the mechanism for generation of DOPAL at aberrant levels and the pathways for toxicity are not conclusively known.

Protein reactivity of 3,4-dihydroxyphenylacetaldehyde, a toxic dopamine metabolite, is dependent on both the aldehyde and the catechol.

Dopamine (DA) has been implicated as an endogenous neurotoxin to explain selective neurodegeneration, as observed for Parkinson's disease (PD). However, previous work demonstrated that 3,4-dihydroxyphenylacetaldehyde (DOPAL) was more toxic than DA. DOPAL is generated as a part of DA catabolism via the activity of monoamine oxidase, and the mechanism of DOPAL toxicity is proposed to involve protein modification.