3,4-Dihydroxyphenylacetaldehyde

Dopaminergic neurotoxicity

DOPAL is known to be a dopaminergic neurotoxin. It is much more potent in this regard than dopamine itself and other metabolites of dopamine. According to the catecholaldehyde hypothesis, DOPAL plays a role in aging-related dopaminergic neurodegeneration and in the pathogenesis of Parkinson's disease. DOPAL is detoxified mainly by aldehyde dehydrogenase (ALDH). DOPAL is a metabolite of dopamine formed by monoamine oxidase (MAO). In differentiated neuronal cells of the PC12 line, physiological concentrations of DOPAL in isolated mitochondria were highly potent in inducing a pathway associated with programmed cell death (or apoptosis), permeability transition. This suggests the cytotoxity of DOPAL and its role in the progression of Parkinson's disease, which has long been associated with mitochondrial abnormalities and neurotoxicity by way of dopaminergic compounds, while reducing the emphasis on other dopamine derivatives and metabolites.

Aldehyde dehydrogenase inhibitors (ALDH inhibitors), which prevent the catabolism of DOPAL and thereby increase DOPAL levels, can produce dopaminergic neurotoxicity or augment dopaminergic neurodegeneration. Examples of ALDH inhibitors include disulfiram and other known dopaminergic neurotoxins including benomyl, daidzin, dieldrin, methylmercury, rotenone, and ziram. DOPAL itself is also known to inhibit ALDH at high concentrations (5μM).

References

References

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