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• W2989563826 endingPage "194" @default.
• W2989563826 startingPage "182" @default.
• W2989563826 abstract "The anthelmintic drug PZQ is the key drug for treating schistosomiasis and several other diseases caused by parasitic flatworms. Despite decades of clinical usage, no flatworm target for PZQ has been convincingly defined – a long-standing roadblock in this field. A calcium-permeable ion channel in Schistosoma mansoni, activated by PZQ, has recently been identified. The characteristics of this channel mirror key features of PZQ action on schistosome muscle. This ion channel is a member of the transient receptor potential melastatin (TRPM) channel subfamily which is broadly expressed in PZQ-sensitive flatworms. This discovery will help to decipher how PZQ perturbs schistosome calcium homeostasis and the ensuing relevance to clinical activity. Infections caused by parasitic flatworms impose a considerable worldwide health burden. One of the most impactful is schistosomiasis, a disease caused by parasitic blood flukes. Treatment of schistosomiasis has relied on a single drug – praziquantel (PZQ) – for decades. The utility of PZQ as an essential medication is, however, intertwined with a stark gap in our knowledge as to how this drug works. No flatworm target has been identified that readily explains how PZQ paralyzes and damages schistosomes. Recently, a schistosome ion channel was discovered that is activated by PZQ and displays characteristics which mirror key features of PZQ action on schistosomes. Here, the journey to discovery of this target, properties of this ion channel, and remaining questions are reviewed. Infections caused by parasitic flatworms impose a considerable worldwide health burden. One of the most impactful is schistosomiasis, a disease caused by parasitic blood flukes. Treatment of schistosomiasis has relied on a single drug – praziquantel (PZQ) – for decades. The utility of PZQ as an essential medication is, however, intertwined with a stark gap in our knowledge as to how this drug works. No flatworm target has been identified that readily explains how PZQ paralyzes and damages schistosomes. Recently, a schistosome ion channel was discovered that is activated by PZQ and displays characteristics which mirror key features of PZQ action on schistosomes. Here, the journey to discovery of this target, properties of this ion channel, and remaining questions are reviewed. a cellular metabolite and endogenous agonist of TRPM2 channels. ADPR production occurs by many pathways in the cell, including release from mitochondria during oxidative stress, or following apoptotic signaling and DNA damage. the COOH terminus of TRPM2 channels contains a domain with homology to the mitochondrial pyrophosphatase NUDT9. This enzyme binds and cleaves ADPR, establishing the idea that the NUDT9H domain in TRPM2 mediates channel activation after binding ADPR. Recent data, however, implicate further complexities in where ADPR binds to TRPM2 channels, and the catalytic role of this domain. the key drug used for treating schistosomiasis. It has been used clinically for decades owing to its effectiveness against all major Schistosoma species, and its low side-effect profile. Because of these advantages, it has largely supplanted the use of other anthelmintics, for example, oxamniquine, as the mainstay therapeutic. by-products of cell metabolism that play important roles in signal transduction, cell function, and viability. TRPM2 channels act as sensors of cellular redox status via binding of ADPR to stimulate channel opening. an infectious disease caused by parasitic flatworms of the genus Schistosoma. The disease afflicts over 200 million people worldwide in Africa, Asia, and South America. Praziquantel is the key drug therapy. a diverse family of cation channels that fulfill versatile roles in cell signaling and sensory physiology. Broadly expressed in excitable and nonexcitable cells, they display varied cation selectivity and modes of activation. the largest of the six subfamilies of TRP channels, comprising eight distinct channels in humans (TRPM1–TRPM8). Their naming derives from the first member to be cloned (TRPM1) which was isolated from a melanoma cDNA library. TRPM channels can be activated by diverse stimuli (ligands, temperature, voltage) and display a range of permeabilities to Ca2+. TRPM channels are receiving increasing interest as a therapeutic target in a spectrum of human diseases." @default.
• W2989563826 created "2019-12-05" @default.
• W2989563826 creator A5037681035 @default.
• W2989563826 creator A5062737684 @default.
• W2989563826 date "2020-02-01" @default.
• W2989563826 modified "2023-10-10" @default.
• W2989563826 title "The Journey to Discovering a Flatworm Target of Praziquantel: A Long TRP" @default.
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• W2989563826 doi "https://doi.org/10.1016/j.pt.2019.11.002" @default.
• W2989563826 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6937385" @default.
• W2989563826 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31787521" @default.
• W2989563826 hasPublicationYear "2020" @default.
• W2989563826 type Work @default.

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