Abstract
Calcium-activated chloride channels (CaCCs) are widespread chloride channels which rely on calcium activation to perform their functions. In 2008, TMEM16A (also known as anoctamin1, ANO1) was identified as the molecular basis of the CaCCs, which provided the possibility to study the physiological function of CaCCs. TMEM16A is widely expressed in various cells and controls basic physiological functions, including neuronal and cardiac excitability, nerve transduction, smooth muscle contraction, epithelial Cl− secretion and fertilization. However, the abnormal function of TMEM16A may cause a variety of diseases, including asthma, gastrointestinal motility disorder and various cancers. Therefore, TMEM16A is a putative drug target for many diseases, and it is important to determine specific and efficient modulators of TMEM16A channel. In recent years, we and others have screened several natural modulators of TMEM16A against cancers and gastrointestinal motility dysfunction. This article reviews the screening methods, efficacy of TMEM16A modulators and pharmacological effects of TMEM16A modulators on different diseases.
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Acknowledgements
We acknowledge the National Natural Science Foundation of China (Grant No.11735006、11175055 to Y Zhan, 11747610 to HL An, 31600594 to CL Pang, 31400711 to YF Chen), the Natural Science Foundation of Hebei Province of China (Grant No. C2018202302 to YF Chen), the Youth Talent Support Program of Hebei Province of China (Grant No.2013001 to YF Chen), for financial support.
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Anqi Hao and Shuai Guo wrote the manuscript; Yafei Chen revised the manuscript; Sai Shi provided the figure; Xuzhao Wang gave the guidances and suggestions; Yafei Chen, Hailong An and Yong Zhan surpervised the study.
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Hao, A., Guo, S., Shi, S. et al. Emerging Modulators of TMEM16A and Their Therapeutic Potential. J Membrane Biol 254, 353–365 (2021). https://doi.org/10.1007/s00232-021-00188-9
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DOI: https://doi.org/10.1007/s00232-021-00188-9