Oxidation chemistry of catecholamines and neuronal degeneration: an update

A review. Aberrant oxidative pathways of catecholamine neurotransmitters, i.e. dopamine and norepinephrine, are an important biochem. correlate of catecholaminergic neuron loss in some disabling neurodegenerative diseases of the elderly, notably Parkinson's disease. In an oxidative stress setting, under conditions of elevated lipid peroxidn., iron accumulation, impaired mitochondrial functioning and antioxidant depletion, catecholamines are oxidatively converted to the corresponding o-quinones, which may initiate a cascade of spontaneous reactions, including intramol. cyclization, aminoethyl side chain fission and interaction with mol. targets. The overall outcome of the competing pathways may vary depending on contingent factors and the biochem. environment, and may include formation of nitrated derivs., neuromelanin deposition, generation of chain fission products, conjugation with L-Cys leading eventually to cytotoxic responses and altered cellular function. In addn., catecholamines may interact with products of lipid peroxidn. and other species derived from oxidative breakdown of biomols., notably glyoxal and other aldehydes, leading e.g. to tetrahydroisoquinolines via Pictet-Spengler chem. After a brief introductory remark on oxidative stress biochem., the bulk of this review will deal with an overview of the basic chem. pathways of catecholamine oxidn., with special emphasis on the analogies and differences between the central neurotransmitters dopamine and norepinephrine. This chem. will form the basis for a concise discussion of the latest advances in the mechanisms of catecholamine-assocd. neurotoxicity in neuronal degeneration.