Modulation of control mechanisms of dopamine-induced apoptosis — a future approach to the treatment of Parkinson’s disease?

摘要: The cause for the progressive and selective degeneration of dopaminergic (DA) nigrostriatal neurons in Parkinson’s disease (PD) is still unknown. We suggest a novel approach, that links this neuronal degenerative process to inappropriate triggering apoptosis, an active, controlled program cellular self destruction, by excess oxidative stress mediated DA metabolism. In support concept, we found DA, endogenous neurotransmitter, capable initiating apoptosis cultured, postmitotic chick sympathetic neurons, observation further extended other systems (PC-12 cells, cerebellar granular thymocytes, splenocytes). comparing relative apoptosis-triggering potency mononamine neurotransmitters, was be most whereas norepinephrine serotonin had moderate mild effects, respectively. This grading can correlated with involvement relevant (i.e., substantia nigra, locus ceruleus raphe nuclei) PD.