Key result
Recent advances in the cryo-EM structures of human Nav channels provide a molecular basis for their functional mechanisms and offer a path toward structure-based drug discovery for various channelopathies.
Why the study?
Mutations in voltage-gated sodium channels cause channelopathies, and recent cryoelectron microscopic structures provide a path toward structure-based drug discovery.
The review highlights how recent advances in the structural biology of voltage-gated sodium channels can facilitate the development of targeted therapies for various channelopathies, including pain and arrhythmias.
May accelerate structure-based Nav modulator design for channelopathies; leaves open clinical translation pending validation.
Voltage-gated sodium (Nav) channels are critical players in the generation and propagation of action potentials by triggering membrane depolarization. Mutations in Nav channels are associated with a variety of channelopathies, which makes them relevant targets for pharmaceutical intervention. So far, the cryoelectron microscopic structure of the human Nav1.2, Nav1.4, and Nav1.7 has been reported, which sheds light on the molecular basis of functional mechanism of Nav channels and provides a path toward structure-based drug discovery. In this review, we focus on the recent advances in the structure, molecular mechanism and modulation of Nav channels, and state updated sodium channel blockers for the treatment of pathophysiology disorders and briefly discuss where the blockers may be developed in the future.
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Li et al. (2019) conducted a review in Channelopathies (pain, migraine, epilepsy, cardiovascular diseases, etc.). Voltage-gated sodium channel blockers was evaluated. Recent advances in the cryo-EM structures of human Nav channels provide a molecular basis for their functional mechanisms and offer a path toward structure-based drug discovery for various channelopathies.
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