摘要Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system.The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells.In this study,we first established a cellular model of Parkinson's disease using 6-hydroxydopamine.When SH-SY5Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells,their activity was greatly increased.The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells.We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson's disease and in a mouse model of Parkinson's disease.Next,we pretreated cell models of Parkinson's disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson's disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase,a marker of dopamine neurons,was markedly restored,α-synuclein aggregation decreased,and insulin-like growth factor-2 receptor down-regulation was alleviated.Finally,in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase(PI3K)/AKT pathway.These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulin-like growth factor-2,and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3K/AKT pathway.Therefore,insulin-like growth factor-2 may be an useful target for Parkinson's disease treatment.