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

The Schistosoma mansoni transient receptor potential melastatin channel (SmTRPMPZQ) is a parasite-specific ion channel that serves as the primary molecular target for the anthelmintic drug praziquantel (Park et al., 2019, Science). It belongs to the TRPM family of transient receptor potential channels and is characterized by its unique sensitivity to praziquantel, which does not affect human TRPM channels (Le et al., 2021, Nature). Upon activation by the drug, SmTRPMPZQ facilitates a massive influx of calcium ions into the schistosome, causing immediate spastic paralysis and severe disruption of the parasite's protective outer layer, the tegument (Park et al., 2019, Science). This mechanism exposes the parasite to the host's immune system, leading to its elimination from the host's circulatory system (Le et al., 2021, Nature). Understanding this target is crucial for addressing praziquantel resistance and developing next-generation treatments for schistosomiasis, a major neglected tropical disease (World Health Organization, 2023). The channel's structure reveals a specific binding pocket for praziquantel, providing a template for structure-based drug design to overcome potential resistance (Le et al., 2021, Nature).

Other names

Praziquantel-activated TRP channelSmTRPMSchistosoma TRPM channelParasite TRPMPZQ

Praziquantel acts as an allosteric agonist that binds to the SmTRPMPZQ channel, inducing a rapid and sustained influx of calcium ions into the parasite. This calcium overload leads to intense muscle contraction (spastic paralysis) and damage to the parasite's tegument, eventually resulting in the death and clearance of the worm by the host's immune system.