ASIC1a 的调节剂及其作为年龄相关性疾病治疗靶点的潜力。

Modulators of ASIC1a and its potential as a therapeutic target for age-related diseases.

作者信息

Zhou Ren-Peng, Liang Hong-Yu, Hu Wei-Rong, Ding Jie, Li Shu-Fang, Chen Yong, Zhao Ying-Jie, Lu Chao, Chen Fei-Hu, Hu Wei

机构信息

Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei 230601, China; The Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Hefei 230032, China.

The Second School of Clinical Medicine, Anhui Medical University, Hefei 230032, China.

出版信息

Ageing Res Rev. 2023 Jan;83:101785. doi: 10.1016/j.arr.2022.101785. Epub 2022 Nov 9.

Abstract

Age-related diseases have become more common with the advancing age of the worldwide population. Such diseases involve multiple organs, with tissue degeneration and cellular apoptosis. To date, there is a general lack of effective drugs for treatment of most age-related diseases and there is therefore an urgent need to identify novel drug targets for improved treatment. Acid-sensing ion channel 1a (ASIC1a) is a degenerin/epithelial sodium channel family member, which is activated in an acidic environment to regulate pathophysiological processes such as acidosis, inflammation, hypoxia, and ischemia. A large body of evidence suggests that ASIC1a plays an important role in the development of age-related diseases (e.g., stroke, rheumatoid arthritis, Huntington's disease, and Parkinson's disease.). Herein we present: 1) a review of ASIC1a channel properties, distribution, and physiological function; 2) a summary of the pharmacological properties of ASIC1a; 3) and a consideration of ASIC1a as a potential therapeutic target for treatment of age-related disease.

摘要

随着全球人口老龄化,与年龄相关的疾病变得越来越普遍。这类疾病涉及多个器官,伴有组织退化和细胞凋亡。迄今为止,对于大多数与年龄相关的疾病,普遍缺乏有效的治疗药物,因此迫切需要确定新的药物靶点以改善治疗效果。酸敏感离子通道1a(ASIC1a)是一种退化蛋白/上皮钠通道家族成员,它在酸性环境中被激活,以调节诸如酸中毒、炎症、缺氧和缺血等病理生理过程。大量证据表明,ASIC1a在与年龄相关疾病(如中风、类风湿性关节炎、亨廷顿病和帕金森病)的发生发展中起重要作用。在此,我们呈现:1)对ASIC1a通道特性、分布和生理功能的综述;2)ASIC1a药理学特性的总结;3)以及将ASIC1a视为治疗与年龄相关疾病的潜在治疗靶点的思考。

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