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The evolution of pentameric ligand-gated ion-channels and the changing family of anthelmintic drug targets

机译：五聚体配体门离子通道的演变和驱虫药靶标的变化家族

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摘要

Pentameric ligand-gated ion-channels rapidly transduce synaptic neurotransmitter signals to an electrical response in postsynaptic neuronal or muscle cells and control the neuromusculature of a majority of multicellular animals. A wide range of pharmaceuticals target these receptors including ethanol, nicotine, anti-depressants and other mood regulating drugs, compounds that control pain and mobility and are targeted by a majority of anthelmintic drugs used to control parasitic infection of humans and livestock. Major advances have been made in recent years to our understanding of the structure, function, activity and the profile of compounds that can activate specific receptors. It is becoming clear that these anthelmintic drug targets are not fixed, but differ in significant details from one nematode species to another. Here we review what is known about the evolution of the pentameric ligand-gated ion-channels, paying particular attention to the nematodes, how we can infer the origins of such receptors and understand the factors that determine how they change both over time and from one species to another. Using this knowledge provides a biological framework in which to understand these important drug targets and avenues to identify new receptors and aid the search for new anthelmintic drugs.
机译：五聚体配体门控离子通道在突触后神经元或肌肉细胞中迅速将突触神经递质信号转导为电响应，并控制大多数多细胞动物的神经肌肉组织。多种药物针对这些受体，包括乙醇，尼古丁，抗抑郁药和其他调节情绪的药物，控制疼痛和活动性的化合物，并被大多数用于控制人和牲畜寄生虫感染的驱虫药所靶向。近年来，我们对可激活特定受体的化合物的结构，功能，活性和概况的了解已取得重大进展。显然，这些驱虫药的靶标不是固定的，而是在一个线虫物种到另一个线虫物种的重要细节上有所不同。在这里，我们回顾了有关五聚体配体门控离子通道进化的已知信息，特别关注了线虫，我们如何推断此类受体的起源，并了解了决定它们随时间和从一个开始如何变化的因素。种到另一个。利用这些知识，可以提供一个生物学框架，在其中可以理解这些重要的药物靶标和途径，以识别新的受体并帮助寻找新的驱虫药。

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