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通过钠通道调节的 conotoxin 的神经生物学活性。

Neurobiological activity of conotoxins via sodium channel modulation.

机构信息

Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121, Naples, Italy.

Department of Sciences, University of Basilicata, 85100, Potenza, Italy.

出版信息

Toxicon. 2020 Nov;187:47-56. doi: 10.1016/j.toxicon.2020.08.019. Epub 2020 Aug 30.

Abstract

Conotoxins (CnTX) are bioactive peptides produced by marine molluscs belonging to Conus genus. The biochemical structure of these venomous peptides is characterized by a low number of amino acids linked with disulfide bonds formed by a high degree of post-translational modifications and glycosylation steps which increase the diversity and rate of evolution of these molecules. CnTX different isoforms are known to target ion channels and, in particular, voltage-gated sodium (Na) channels (Na channels). These are transmembrane proteins fundamental in excitable cells for generating the depolarization of plasma membrane potential known as action potential which propagates electrical signals in muscles and nerves for physiological functions. Disorders in Na channel activity have been shown to induce neurological pathologies and pain states. Here, we describe the current knowledge of CnTX isoform modulation of the Na channel activity, the mechanism of action and the potential therapeutic use of these toxins in counteracting neurological dysfunctions.

摘要

短肽(conotoxin, CnTX)是海洋贝类动物芋螺属 (Conus) 产生的生物活性肽。这些毒液肽的生化结构特征是氨基酸数量较少,通过高度的翻译后修饰和糖基化步骤形成二硫键,从而增加了这些分子的多样性和进化速度。已知 CnTX 的不同亚型可靶向离子通道,特别是电压门控钠 (Na) 通道 (Na 通道)。这些通道是在可兴奋细胞中产生称为动作电位的细胞膜电位去极化的跨膜蛋白,动作电位在肌肉和神经中传播电信号以实现生理功能。Na 通道活性的紊乱已被证明会引发神经病理学和疼痛状态。在这里,我们描述了 CnTX 亚型对 Na 通道活性的调节、作用机制以及这些毒素在对抗神经功能障碍方面的潜在治疗用途的最新知识。

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