Synuclein-1 is selectively up-regulated in response to nerve growth factortreatment in PC12 cells

Mutations in the alpha -synuclein gene have recently been identified in fam ilies with inherited Parkinson's disease and the protein product of this ge ne is a component of Lewy bodies, indicating that alpha -synuclein is invol ved in Parkinson's disease pathogenesis. A role for normal alpha -synuclein in synaptic function, apoptosis or plasticity responses has been suggested . We show here that in rat pheochromocytoma PC12 cells synuclein-1, the rat homolog of human alpha -synuclein, is highly and selectively up-regulated at the mRNA and protein levels after 7 days of nerve growth factor treatmen t. Synuclein-1 expression appears neither sufficient nor necessary for the neuritic sprouting that occurs within 1-2 days of nerve growth factor treat ment. Rather, it likely represents a component of a late neuronal maturatio nal response. Synuclein-1 redistributes diffusely within the cell soma and the neuritic processes in nerve growth factor-treated PC12 cells. Cultured neonatal rat sympathetic neurones express high levels of synuclein-1, with a diffuse intracellular distribution, similar to neuronal PC12 cells. These results suggest that levels of synuclein-1 may be regulated by neurotrophi c factors in the nervous system and reinforce a role for alpha -synuclein i n plasticity-maturational responses. In contrast, there is no correlation b etween synuclein expression and apoptotic death following trophic deprivati on.