Hippo/YAP信号通路在神经系统中的作用及机制研究进展

The roles and mechanisms of the Hippo/YAP signaling pathway in the nervous system

Hippo信号通路高度保守,由一系列激酶级联反应构成,主要通过下游效应分子YAP(Yes-associated protein)/TAZ(transcriptional coactivator with PDZ-binding motif)转录辅激活因子调控细胞增殖、凋亡和分化等活动,从而控制器官大小和组织发育稳态。在正常发育情况下,神经细胞数目、空间分布的精准调控对于大脑发育至关重要。近年来研究发现,Hippo/YAP信号通路在神经干细胞增殖分化、神经元前体细胞增殖、胶质细胞分化和激活、髓鞘化发育以及神经系统疾病的发生发展等方面发挥重要作用。因此,有必要对该信号通路在神经系统中的作用和机制进行深入系统地研究。本文对Hippo/YAP信号通路在神经系统中的最新研究进展进行了综述,以期为神经系统发育和神经损伤疾病的治疗提供理论基础。

The Hippo signaling pathway, consisting of a highly conserved kinase cascade and downstream transcription co-activators YAP(Yes-associated protein)/TAZ(transcriptional coactivator with PDZ-binding motif), plays a key role in tissue homeostasis and organ size control by regulating the proliferation, differentiation and apoptosis of cells. During normal development, the precise control of neural cell numbers and spatial distributions of these neural cells is important for brain development. Recent studies have shown that the Hippo/YAP signaling pathway isactt ively involved d in the self-re enewal of neurr al stem cells, p proliferation oo f neural progee nitor cells, dif fferentiation ann d actt ivation of glia al cells, and m yelination of gg lial cells as w well as in the dd evelopment off neurological diseases. Due to its prominent rol e in the nervou us system, it is necessary to f further study o n this pathwayy. In this review w, we summarii ze thee recent studies s and focus on n the roles and mechanisms o of the Hippo/YAA P signaling pp athway in the nervous systemm, andd provide insig ghts for neural development aa nd neural inju ury diseases.