Transient receptor potential(TRP)channels are sensors for a variety of cellular and environmental signals.Mammals express a total of 28 different TRP channel proteins,which can be divided into seven subfamilies based ...Transient receptor potential(TRP)channels are sensors for a variety of cellular and environmental signals.Mammals express a total of 28 different TRP channel proteins,which can be divided into seven subfamilies based on amino acid sequence homology:TRPA(Ankyrin),TRPC(Canonical),TRPM(Melastatin),TRPML(Mucolipin),TRPN(NO-mechano-potential,NOMP),TRPP(Polycystin),TRPV(Vanilloid).They are a class of ion channels found in numerous tissues and cell types and are permeable to a wide range of cations such as Ca^(2+),Mg^(2+),Na^(+),K^(+),and others.TRP channels are responsible for various sensory responses including heat,cold,pain,stress,vision and taste and can be activated by a number of stimuli.Their predominantly location on the cell surface,their interaction with numerous physiological signaling pathways,and the unique crystal structure of TRP channels make TRPs attractive drug targets and implicate them in the treatment of a wide range of diseases.Here,we review the history of TRP channel discovery,summarize the structures and functions of the TRP ion channel family,and highlight the current understanding of the role of TRP channels in the pathogenesis of human disease.Most importantly,we describe TRP channel-related drug discovery,therapeutic interventions for diseases and the limitations of targeting TRP channels in potential clinical applications.展开更多
基金This work was supported by grants from the National Key Research and Development Program of China(2022YFC2303504)the Program of the Shanghai Committee of Science and Technology,China(21ZR1475200 and 22ZR1469900)+2 种基金the National Natural Science Foundation of China(92157106,32270917)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDPB16)Shanghai Municipal Science and Technology Major Project(2019SHZDZX02).
文摘Transient receptor potential(TRP)channels are sensors for a variety of cellular and environmental signals.Mammals express a total of 28 different TRP channel proteins,which can be divided into seven subfamilies based on amino acid sequence homology:TRPA(Ankyrin),TRPC(Canonical),TRPM(Melastatin),TRPML(Mucolipin),TRPN(NO-mechano-potential,NOMP),TRPP(Polycystin),TRPV(Vanilloid).They are a class of ion channels found in numerous tissues and cell types and are permeable to a wide range of cations such as Ca^(2+),Mg^(2+),Na^(+),K^(+),and others.TRP channels are responsible for various sensory responses including heat,cold,pain,stress,vision and taste and can be activated by a number of stimuli.Their predominantly location on the cell surface,their interaction with numerous physiological signaling pathways,and the unique crystal structure of TRP channels make TRPs attractive drug targets and implicate them in the treatment of a wide range of diseases.Here,we review the history of TRP channel discovery,summarize the structures and functions of the TRP ion channel family,and highlight the current understanding of the role of TRP channels in the pathogenesis of human disease.Most importantly,we describe TRP channel-related drug discovery,therapeutic interventions for diseases and the limitations of targeting TRP channels in potential clinical applications.