Research progress on PIEZO1 protein structure and activation mechanism by small-molecule agonists

Piezo1, a non-selective cation channel, can transduce diverse mechanical stimuli into electrochemical signals and perform essential physiological functions in the human body. Anomalous Piezo1 activities due to loss-of-function mutations are linked to diverse pathological states ranging from anemia,...

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Main Authors: Danjiang Li, Yuanyuan Song, Yuan Zeng, Hua Hu, Wei Tian
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Results in Chemistry
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211715625000414
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author Danjiang Li
Yuanyuan Song
Yuan Zeng
Hua Hu
Wei Tian
author_facet Danjiang Li
Yuanyuan Song
Yuan Zeng
Hua Hu
Wei Tian
author_sort Danjiang Li
collection DOAJ
description Piezo1, a non-selective cation channel, can transduce diverse mechanical stimuli into electrochemical signals and perform essential physiological functions in the human body. Anomalous Piezo1 activities due to loss-of-function mutations are linked to diverse pathological states ranging from anemia, malaria immunity, lymphatic abnormalities, and varicose veins. Thus, targeting and modulating Piezo1 have demonstrated the potential to yield significant therapeutic benefits, thereby affirming Piezo1 as a promising drug target for various diseases. Recent studies have unveiled crystal structures of Piezo1 and identified small-molecule agonists that shed light on the channel’s structure and activation mechanism. This review consolidates our understanding of Piezo1, focusing on its structural features, mechanosensitive activation and potential agonists to guide future investigations in this field.
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series Results in Chemistry
spelling doaj-art-ec1b2137093d49619ed40dbfa336636d2025-08-20T01:58:28ZengElsevierResults in Chemistry2211-71562025-03-011410205810.1016/j.rechem.2025.102058Research progress on PIEZO1 protein structure and activation mechanism by small-molecule agonistsDanjiang Li0Yuanyuan Song1Yuan Zeng2Hua Hu3Wei Tian4Central Theater General Hospital, Wuhan 430070 ChinaCentral Theater General Hospital, Wuhan 430070 ChinaCentral Theater General Hospital, Wuhan 430070 ChinaCorresponding authors.; Central Theater General Hospital, Wuhan 430070 ChinaCorresponding authors.; Central Theater General Hospital, Wuhan 430070 ChinaPiezo1, a non-selective cation channel, can transduce diverse mechanical stimuli into electrochemical signals and perform essential physiological functions in the human body. Anomalous Piezo1 activities due to loss-of-function mutations are linked to diverse pathological states ranging from anemia, malaria immunity, lymphatic abnormalities, and varicose veins. Thus, targeting and modulating Piezo1 have demonstrated the potential to yield significant therapeutic benefits, thereby affirming Piezo1 as a promising drug target for various diseases. Recent studies have unveiled crystal structures of Piezo1 and identified small-molecule agonists that shed light on the channel’s structure and activation mechanism. This review consolidates our understanding of Piezo1, focusing on its structural features, mechanosensitive activation and potential agonists to guide future investigations in this field.http://www.sciencedirect.com/science/article/pii/S2211715625000414ProgressPiezo1StructureMechanismAgonist
spellingShingle Danjiang Li
Yuanyuan Song
Yuan Zeng
Hua Hu
Wei Tian
Research progress on PIEZO1 protein structure and activation mechanism by small-molecule agonists
Results in Chemistry
Progress
Piezo1
Structure
Mechanism
Agonist
title Research progress on PIEZO1 protein structure and activation mechanism by small-molecule agonists
title_full Research progress on PIEZO1 protein structure and activation mechanism by small-molecule agonists
title_fullStr Research progress on PIEZO1 protein structure and activation mechanism by small-molecule agonists
title_full_unstemmed Research progress on PIEZO1 protein structure and activation mechanism by small-molecule agonists
title_short Research progress on PIEZO1 protein structure and activation mechanism by small-molecule agonists
title_sort research progress on piezo1 protein structure and activation mechanism by small molecule agonists
topic Progress
Piezo1
Structure
Mechanism
Agonist
url http://www.sciencedirect.com/science/article/pii/S2211715625000414
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