G蛋白耦联受体17在中枢神经系统的多功能调控机制及治疗转化

Multifunctional regulatory mechanisms and therapeutic translation of G protein-coupled receptor 17 in central nervous system

  • 摘要: G蛋白耦联受体17(GPR17)是一种G蛋白耦联受体,其功能多样性由受体二聚化与表观遗传修饰等多重机制调控,参与神经系统发育、损伤修复及多种神经疾病的发展进程。本文整合神经发育-损伤修复-代谢调控三维功能网络,阐释GPR17在神经系统中的正常发育过程及病理进程。在神经系统中, GPR17参与少突胶质谱系细胞的命运调控及小胶质细胞的活化,并对神经前体细胞和成年神经组织的多能性调节产生影响。在脱髓鞘疾病、脑损伤、脑胶质瘤等神经病理状态下, GPR17表达异常,抑制其表达可缓解髓鞘损伤,激活其表达可诱导胶质瘤细胞分化凋亡。此外, GPR17还参与调节代谢、衰老及认知功能障碍。尽管当前研究已取得一定进展,但其发育期信号转导机制及在神经疾病中的具体作用路径仍需深入探索。鉴于GPR17在神经系统中的多功能性与关键作用,该领域有望为神经发育、损伤修复及相关疾病治疗提供全新思路与治疗策略。

     

    Abstract: G protein-coupled receptor 17 (GPR17) is a G protein-coupled receptor whose functional diversity is regulated by multiple mechanisms, including receptor dimerization and epigenetic modifications. It is involved in the development of the nervous system, injury repair, and the progression of various neurological diseases. This study integrated a three-dimensional functional network of neurodevelopment-injury repair-metabolic regulation to elucidate the normal developmental process and pathological progression of GPR17 in the nervous system. In the nervous system, GPR17 participates in the fate regulation of oligodendrocyte lineage cells and the activation of microglia, and also affects the pluripotency regulation of neural precursor cells and adult neural tissues. Under neuropathological conditions such as demyelinating diseases, brain injuries, and gliomas, GPR17 expression is abnormal. Inhibiting its expression can alleviate myelin sheath damage, while activating its expression can induce the differentiation and apoptosis of glioma cells. Additionally, GPR17 is involved in the regulation of metabolism, aging, and cognitive dysfunction. Although significant progress has been made in current research, the signal transduction mechanisms during development and the specific action pathways in neurological diseases still require further exploration. Given the multifunctionality and key role of GPR17 in the nervous system, this field holds promise for providing novel ideas and therapeutic strategies for neural development, injury repair, and the treatment of related diseases.

     

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