α-Synuclein is an abundant neuronal protein of uncertain function linked to Parkinson's disease. Numerous studies have proposed an antiapoptotic function forα-synuclein, based on overexpression experiments in cell lines. To explore whetherα-synuclein has such a physiological function, we assessed the response of wild type orα-synuclein null neonatal mouse sympathetic neurons to nerve growth factor deprivation, a well-characterized stimulus of neuronal apoptosis. There was no difference in the rate of neuronal loss, neuronal apoptosis, or c-jun phosphorylation. Furthermore, the absence ofα-synuclein did not alter the magnitude of naturally occurring cell deathin vivoin substantia nigra pars compacta. Therefore,α-synuclein is unlikely to play a significant role in apoptotic signalling in catecholaminergic neurons of the neonatal nervous system. [ABSTRACT FROM AUTHOR]