TRP 下降,TRP 下降:稳定的反染色体目标照明嗒嗒声

Daniel J. Sprague, C. Rohr, Jonathan S. Marchant
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引用次数: 0

摘要

由寄生扁虫引起的感染给疾病带来了沉重负担。被忽视的热带疾病血吸虫病就是一个很好的例子,它困扰着全世界数百万人。几十年来,人们已经知道各种化学药物具有抗血吸虫活性,但其中许多药物的寄生虫靶点仍未确定。直到最近,目前的临床疗法吡喹酮 (PZQ) 也是如此。不过,靶点发现的步伐最近加快了,发现了吡喹酮(PZQ)和抗蠕虫药苯二氮卓--美氯硝西泮(MCLZ)的血吸虫靶点。这种稳定的靶点模式还揭示了一个规律,即 PZQ 和 MCLZ 的靶点都属于同一个离子通道亚群--美拉司他丁家族瞬时受体电位离子通道(TRPM 通道)。PZQ 激活该家族的一个成员(TRPMPZQ),而 MCLZ 激活另一个不同的通道(TRPMMCLZ)。本文讨论了这两个新靶点的异同。鉴于寄生扁形虫容易受到化疗药物的攻击,这些数据强调了进一步研究寄生扁形虫体内 TRPM 通道的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TRP drop, TRP drop: a steady patter of anti-schistosomal target illumination
Infections caused by parasitic flatworms impart a significant disease burden. This is well exemplified by the neglected tropical disease schistosomiasis, which afflicts millions of people worldwide. The anti-schistosomal activity of various chemotypes has been known for decades, but the parasite targets of many of these remain undefined. Until recently, this included the current clinical therapy, praziquantel (PZQ). However, the tempo of target discovery has recently gathered pace, with discoveries of schistosome targets for praziquantel (PZQ) and the anthelmintic benzodiazepine, meclonazepam (MCLZ). This steady patter of target illumination has also revealed a pattern in that both PZQ and MCLZ target members of the same ion channel subgroup—transient receptor potential ion channels of the melastatin family (TRPM channels). PZQ activates one member of this family (TRPMPZQ) and MCLZ activates a different channel (TRPMMCLZ). Here, similarities and differences between these two new targets are discussed. These data highlight the need for further study of TRPM channels in parasitic flatworms given their vulnerability to chemotherapeutic attack.
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