Rescue of alpha-synuclein cytotoxicity by insulin-like growth factors.

While mutation of alpha-synuclein is a cause of autosomal-dominant Parkinson's disease (PD), it is still elusive as to how alpha-synuclein is involved in the pathogenesis of PD. Here, we show that dopamine-dependent accumulation of alpha-synuclein in cultured cells results in apoptosis. Furthermore, activation of insulin-like growth factor 1 (IGF-1) pathway can rescue alpha-synuclein toxicity and suppress alpha-synuclein aggregation through the activation of PI3K/Akt pathways. These results suggest the therapeutic potential of IGF-1 pathway in Parkinson disease.