Schistosoma mansoni transient receptor potential melastatin-like channel (Sm.TRPMPZQ) (Sm.TRPMPZQ)

Schistosoma mansoni transient receptor potential melastatin-like channel (Sm.TRPMPZQ) is a specialized ion channel identified as the primary molecular target of the anthelmintic drug praziquantel (Park et al., 2019, Science). It belongs to the TRPM (melastatin) subfamily of transient receptor potential channels but possesses a unique binding pocket that confers sensitivity to praziquantel, a feature absent in human TRPM counterparts (Le et al., 2023, Nature). The channel's primary biological function in the parasite involves regulating calcium homeostasis, which is critical for neuromuscular coordination and the integrity of the tegument (Park et al., 2019). When praziquantel binds to Sm.TRPMPZQ, it acts as a potent agonist, causing the channel to remain open and allowing a massive influx of extracellular calcium (Le et al., 2023). This sudden increase in intracellular calcium leads to rapid, sustained muscle contraction (paralysis) and vacuolization of the parasite's surface, exposing it to host immune attack (Park et al., 2019). Understanding this target is crucial for addressing schistosomiasis, a major neglected tropical disease, and for developing next-generation anthelmintics to combat potential drug resistance. This target is highly specific to schistosomes and related flatworms, making it an ideal candidate for selective toxicity (Park et al., 2019).

Other names

SmTRPMPZQPraziquantel-activated TRP channelSchistosoma mansoni TRPM channel

Agonist-induced activation leading to rapid calcium influx, parasite paralysis, and tegumental disruption.