Ras, a eukaryotic intracellular protein integrates extracellular signals from multiple receptor types. The aim was to unravel the role of Ras in dopaminergic neurons. To obtain initial insight, differentiated embryonic midbrain neurospheres were
characterized and significant increase in the number of dopaminergic neurons was observed in synRas derived cultures compared to wildtype. Pronounced neuroprotection was observed in synRas cultures. Cell death via apoptotic dependent and independent
mechanisms was found to be drastically reduced in synRas derived cultures. Enhanced neuronal expression of Ras elevated phosphorylation of its downstream effectors MAPK, Akt, Bad and CREB. Enhanced transcriptional activity of TH promoter was observed in
synRas cultures. Dopamine production and electrical characteristics of dopaminergic neurons was confirmed by HPLC and electrophysiological studies, thereby confirming that Ras enhances and stabilizes dopaminergic properties.