Reduced neuritic outgrowth and cell adhesion in neuronal cells transfected with human α-synuclein

Since recent reports have suggested that alpha -synuclein might play a role in neuronal plasticity, the main objective of this study was to determine the effects of alpha -synuclein on neuritic outgrowth. We stably transfected either human (h) alpha- or beta -synuclein cDNA in B103 rat neuronal cells. Expression of h alpha -synuclein resulted in reduced neurite extension and weak adhesion compared to vector-transfected and h beta -synuclein expressing cells. To investigate the potential pathways involved, we studied the effects of reagents known to modulate B103 proliferation and differentiation. Neither phorbol 12-myristate 13-acetate nor forskolin or antioxidants (catalase, superoxide dismutase, or vitamin E) were able to restore the reduced length of neurites in h alpha -synuclein-expressing cells. These results suggest that reduced neuritic activity in the h alpha -synuclein-expressing cells might be due, in part, to alterations in cell adhesion capacity. This might be attributed to alpha -synuclein affecting a signal transduction pathway distinct from protein kinase C and protein kinase A.