Orbeli Institute of Physiology, National Academy of Sciences of the Republic of Armenia, Yerevan, Armenia.
Department of Medical Genetics, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Praha 10, Czech Republic.
Drug Discov Today. 2019 Oct;24(10):1968-1984. doi: 10.1016/j.drudis.2019.06.012. Epub 2019 Jun 24.
The neuromuscular junction (NMJ) is the principal site for the translation of motor neurochemical signals to muscle activity. Therefore, the release and sensing machinery of acetylcholine (ACh) along with muscle contraction are two of the main targets of natural toxins and pathogens, causing paralysis. Given pharmacology and medical advances, the active ingredients of toxins that target postsynaptic mechanisms have become of major interest, showing promise as drug leads. Herein, we review key facets of prevalent toxins modulating the mechanisms of ACh sensing and generation of the postsynaptic response, with muscle contraction. We consider the correlation between their outstanding selectivity and potency plus effects on motor function, and discuss emerging data advocating their usage for the development of therapies alleviating neuromuscular dysfunction.
神经肌肉接头（NMJ）是将运动神经化学信号转化为肌肉活动的主要部位。因此，乙酰胆碱（ACh）的释放和感应机制以及肌肉收缩是天然毒素和病原体的两个主要靶点，导致瘫痪。鉴于药理学和医学的进步，靶向突触后机制的毒素的有效成分已成为主要关注点，有望成为药物先导物。本文综述了调节 ACh 感应和产生突触后反应的机制的流行毒素的关键方面，以及与肌肉收缩的关系。我们考虑了它们出色的选择性和效力以及对运动功能的影响之间的相关性，并讨论了支持将其用于开发缓解神经肌肉功能障碍的疗法的数据。
