Insulin-like growth factor-1 protects human dopaminergic SH-SY5Y cells from salsolinol-induced toxicity.

Parkinson's disease (PD) is characterized by an extensive loss of dopaminergic neurons in the substantia nigra pars compacta. Salsolinol (SAL), a dopamine-derived tetrahydroisoquinoline, has been suspected to be involved in the etiology of PD. In the present study, the neuroprotective effect of insulin-like growth factor-1 (IGF-1) was studied against SAL-induced toxicity in human dopaminergic SH-SY5Y cells. SAL (100 microM) decreased cell viability in SH-SY5Y cells significantly after 24 h exposure. Both exogenous IGF-1 and IGF-1 gene transfer significantly prevented the SAL-induced cell death and increased cell viability. Wortmannin, a specific phosphatidylinositol-3-kinase (PI-3 kinase) inhibitor, completely blunted the IGF-1-induced neuroprotection, suggesting that PI-3 kinase pathway is critical in mediating the neuroprotective effects of IGF-1. These results suggest that IGF-1 may be a useful growth factor in the treatment of PD. Copyright 2003 Elsevier Science Ireland Ltd.