Schistosome transient receptor potential melastatin praziquantel-activated channel (TRPM_PZQ)

The Schistosome transient receptor potential melastatin praziquantel-activated channel (TRPM_PZQ) is a specialized ion channel found in parasitic flatworms of the genus Schistosoma (Park et al., 2019). It serves as the primary molecular target for praziquantel, the gold-standard drug used to treat schistosomiasis globally (Marchant et al., 2020). TRPM_PZQ functions as a non-selective cation channel that, upon activation, allows a massive influx of calcium ions into the parasite's cells (Le et al., 2021). This sudden increase in intracellular calcium triggers rapid, sustained muscle contraction and paralysis, as well as severe damage to the worm's protective outer layer, the tegument (Park et al., 2019). These physiological changes lead to the detachment of the worms from the host's blood vessel walls and their subsequent clearance by the host's immune system (Marchant et al., 2020). While TRPM channels are conserved across many species, the specific structural features that allow praziquantel binding are unique to schistosomes and related trematodes, providing a high degree of therapeutic selectivity (Le et al., 2021). Understanding this target is crucial for monitoring potential drug resistance and developing next-generation anthelmintics that can overcome the current limitations of praziquantel, such as its reduced efficacy against juvenile parasites (Marchant et al., 2020).

Other names

SmTRPM_PZQPraziquantel-activated TRP channelSchistosoma mansoni TRPM channelPraziquantel target channel

Allosteric activation of the TRPM_PZQ channel leading to rapid and massive calcium ion influx into the parasite