Piezo-Type Mechanosensitive Ion Channel Component 1 (Piezo1): APromising Therapeutic Target and Its Modulators

Piezo1 is a member of the mechanosensitive piezoion channel family, which transduces various mechanicalstimulations into electrochemical signals. Piezo1 is closelyimplicated in different physiological processes ranging fromerythrocyte volume homeostasis to lymphatic vessel formationand bone homeostasis. Aberrant Piezo1 functions caused by gain-of-function or loss-of-function mutations are associated withvarious pathological conditions. Due to the significant contributionon the recognition of Piezo ion channels for sensing mechanicalstress, Ardem Patapoutian received the 2021 Nobel Prize inPhysiology or Medicine (jointly). Strategies of targeting andmodulating Piezo1 have shown potential to produce significanttherapeutic effects, thus validating Piezo1 as a promising drugtarget for diseases. In this Perspective, we review the cryo-EM structure, mechanogating mechanism, and physiological profiles ofPiezo1, together with the latest advances in the development of its modulators. Limitations and challenges as well as futuredevelopment of Piezo1 modulators are discussed as well.

Automated summary

Piezo1 is a mechanosensitive channel that plays important physiological roles and is associated with various pathological conditions. Targeting and modulating Piezo1 have shown potential therapeutic effects, making it a promising drug target for diseases.