Impact of Dopamine Oxidation on Dopaminergic Neurodegeneration

Parkinson's disease (PD) is the second most common neurodegenerative disease. The characteristic feature of PD is the progressive degeneration of the dopaminergic (DAergic) neurons in the substantia nigra (SN). DAergic neurons in the SN accumulate black and insoluble membrane structures known as neuromelanin during aging. The oxidation of dopamine (DA) to form neuromelanin generates many o-quinones, including DA o-quinones, aminochrome, and 5,6-indolequinone. The focus of this review is to discuss the role of DA oxidation in association with PD. The oxidation of DA produces oxidative products, inducing mitochondrial dysfunction, impaired protein degradation, alpha-synuclein aggregation into neurotoxic oligomers, and oxidative stress, in vitro. Recent studies have demonstrated that the DA content is critical for both DJ-1 knockout and A53T alpha-synuclein transgenic mice to develop PD pathological features, providing evidence for DA action in PD pathogenesis in vivo. The effects of L-DOPA, as the most effective anti-PD drug, are also briefly discussed.