Schistosoma mansoni transient receptor potential melastatin-like channel (SmTRPMPZQ) (SmTRPMPZQ)

The Schistosoma mansoni transient receptor potential melastatin-like channel (SmTRPMPZQ) is the primary molecular target of praziquantel, the mainstay treatment for schistosomiasis (Park et al., 2019). It is an ion channel belonging to the TRPM family that is uniquely sensitive to praziquantel, which acts as an allosteric agonist. Binding of the drug to the channel's voltage-sensor-like domain triggers a massive influx of calcium ions into the parasite (Le et al., 2021). This calcium overload causes rapid, sustained muscle paralysis and severe damage to the parasite's tegument, leading to its detachment from host tissues and subsequent elimination by the immune system. While highly effective against adult worms, SmTRPMPZQ shows reduced sensitivity or expression in juvenile stages, which contributes to the clinical challenge of treating early-stage infections (Marchant et al., 2020). This target is phylogenetically distinct from human TRP channels, which explains the high therapeutic index of praziquantel. Ongoing research into SmTRPMPZQ aims to identify potential resistance mechanisms and develop new compounds that can target the channel across all life stages of the parasite.

Other names

SmTRPM_PZQPraziquantel-activated TRP channelTRPMPZQSchistosoma mansoni TRPM channel

Allosteric activation (agonism) leading to calcium influx, spastic paralysis, and tegumental damage (Park et al., 2019; Le et al., 2021).