自噬
程序性细胞死亡
细胞生物学
细胞凋亡
基因敲除
基因沉默
PI3K/AKT/mTOR通路
激酶
ULK1
化学
癌症研究
生物
信号转导
蛋白激酶A
安普克
生物化学
基因
作者
Yinying Qin,Junqiang Huang,Xiangyou Zhao
标识
DOI:10.1016/j.cellsig.2022.110328
摘要
The mammalian Ste20-like kinases 1 (Mst1) is essential for regulating cell proliferation, differentiation, apoptosis, and autophagy. However, the molecular mechanisms of Mst1 in neuronal cell death remains incompletely understood. Here, we showed that Mst1 is up-regulated in Parkinson's disease (PD) model induced by MPP+. Knockdown of Mst1 resulted in a reduction in MPP+-induced apoptosis and autophagy in SH-SY5Y and CHP 212 cells. Mechanistically, Mst1 silencing suppressed autophagy by activating mTOR/ULK1/S6K1 pathway. We also showed that miR-135a-5p was lower while Mst1 was inversely higher in MPP+-treated cells. Furthermore, miR-135a-5p has a protective role on MPP+-induced neuronal cell death via targeting Mst1. On the whole, the miR-135a-5p/Mst1 axis might serve as a potential therapeutic target in PD treatment.
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