Is there a rationale for neuroprotection against dopamine toxicity in Parkinson's disease?

Parkinson's disease is a progressive neurological disease caused by rather selective degeneration of the dopaminergic neurons in the substantia nigra. Though subject to intensive research, the etiology of this nigral loss is still undetermined and treatment is basically symptomatic. The current majo r hypothesis is that nigral neuronal death in PD is due to excessive oxidat ive stress generated by auto and enzymatic oxidation of the endogenous neur otransmitter dopamine (DA), the formation of neuromelanin (MM) and the pres ence of a high concentration of iron. In this review article although we co ncisely describe the effects of NM and iron on neuronal survival, we mainly focus on the molecular mechanisms of DA-induced apoptosis, DA exerts its t oxic effects through its oxidative metabolites either in vitro or in vivo T he oxidative metabolites then activate a very intricate web of signals, whi ch culminate in cell death. The signal transduction pathways and genes, whi ch are associated with DA toxicity are described in detail.