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Neuroprotective effects of insulin-like growth factor-2 in 6-hydroxydopamine-induced cellular and mouse models of Parkinson’s disease

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Neural Regeneration Research 2023年第5期18卷 1099-1106页

作者： Hai-Ying Zhang Yong-Cheng Jiang Jun-Rui Li Jia-Nan Yan Xin-Jue Wang Jia-Bing Shen Kai-Fu Ke Xiao-Su Gu Department of Neurology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Research Center of Clinical Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Department of Clinical Medicine The First Clinical Medical College of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina

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-SY5 Y 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 downregulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase(PI3 K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulinlike growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3 K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson’s disease treatment.

关键词： 6-hydroxydopamine alpha-synuclein insulin-like growth factor-2 receptor insulin-like growth factor-2 neurodegeneration neuroprotection Parkinson’s disease skin-derived precursor Schwann cells

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