TRPM7生理病理学功能及其小分子调节剂的发现
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作者单位:

1)中国科学院上海药物研究所,神经精神疾病研究中心,上海 201203;2)中国科学院中山药物创新研究院,中山 528400

作者简介:

高召兵 Tel: 15021912788, E-mail: zbgao@simm.ac.cn郑月明 Tel: 15021104503, E-mail: zhengyueming@simm.ac.cnGAO Zhao-Bing. Tel: 86-15021912788, E-mail: zbgao@simm.ac.cnZHENG Yue-Ming. Tel: 86-15021104503, E-mail: zhengyueming@simm.ac.cn

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基金项目:

国家杰出青年科学基金(81825021) 和中国科学院青年创新促进 会(2020284) 资助项目。


Physiological and Pathological Functions of TRPM7 Channel and Its Small-molecule Modulators
Author:
Affiliation:

1)Center for Neurological and Psychiatric and Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;2)Zhongshan Institute of Drug Discovery, Institution for Drug Discovery Innovation, Chinese Academy of Science, Zhongshan 528400, China

Fund Project:

This work was supported by grants from National Science Fund for Distinguished Young Scholars (81825021), and the Youth Innovation Promotion Association of the Chinese Academy of Sciences (2020284).

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    摘要:

    TRPM7(transient receptor potential melastatin 7)通道属于TRPM亚家族,是一种具有离子通道结构域和激酶结构域的双功能跨膜蛋白。作为非选择性阳离子通道,TRPM7可通透Ca2+、Mg2+、Zn2+、Na+、K+等和其他微量金属离子。TRPM7在人体各组织广泛表达,参与Mg2+的稳态调控、细胞增殖、分化、黏附和迁移等生理过程。临床上,TRPM7功能紊乱与神经退行性疾病、中风、癌症等多种疾病关系密切。本文主要综述TRPM7通道在生理、病理及小分子调节剂方面的研究进展,为相关疾病的药物开发提供新的思路。

    Abstract:

    Transient receptor potential melastatin 7 (TRPM7), a member of the TRPM subfamily, is a ubiquitously expressed bifunctional transmembrane protein with a channel domain fused to an active kinase domain. As a non-selective cation channel, TRPM7 is permeable to Ca2+, Mg2+, Zn2+, Na+, K+, and other trace metals. As an α-kinase, TRPM7 can autophosphorylate its serine and threonine residues, or phosphorylate endogenously targeted substrates such as myosin II. Through the joint action of the two domains, TRPM7 participates in various physiological processes such as Mg2+ homeostasis regulation, cell proliferation, differentiation, adhesion and migration, and ultimately affects cell differentiation and embryonic development. Dysfunction of TRPM7 has been associated with multiple neurodegenerative diseases, tissue fibrosis, ischemic injury as well as the occurrence and development of tumors. Genetic or pharmacological deficit of the TRPM7 relieves ischemic neuronal injury and inhibits the proliferation and migration of tumors, while up-regulating or restoring TRPM7 decreases blood pressure, maintains normal embryonic development and may be an effective strategy to treat the neurodegenerative disorders. However, whether TRPM7 is a promising target for the development of clinical drugs remains elusive. Nowadays, several small molecules display activation or inhibitory activities on the TRPM7 channel, and have been successfully used to uncover new cellular roles of TRPM7 in physiological and pathological conditions. Nonetheless, selective and potent TRPM7 modulators are limited. This review summarizes the research progress on the physiological and pathological functions of TRPM7 and its small-molecule modulators, which may provide new therapeutic strategies for TRPM7-related diseases and new directions for the development of novel TRPM7 regulators.

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王云起,官子月,高召兵,郑月明. TRPM7生理病理学功能及其小分子调节剂的发现[J].生物化学与生物物理进展,2023,50(12):2856-2868

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历史
  • 收稿日期:2022-10-26
  • 最后修改日期:2023-10-18
  • 接受日期:2023-03-23
  • 在线发布日期: 2023-12-22
  • 出版日期: 2023-12-20