Billen Bert, Bosmans Frank, Tytgat Jan
Laboratory of Toxicology, KULeuven, Campus Gasthuisberg O&N 2, PO Box 922, Herestraat 49, 3000 Leuven, Belgium.
Curr Pharm Des. 2008;14(24):2492-502. doi: 10.2174/138161208785777423.
Throughout millions of years of evolution, nature has supplied various organisms with a massive arsenal of venoms to defend themselves against predators or to hunt prey. These venoms are rich cocktails of diverse bioactive compounds with divergent functions, extremely effective in immobilizing or killing the recipient. In fact, venom peptides from various animals have been shown to specifically act on ion channels and other cellular receptors, and impair their normal functioning. Because of their key role in the initiation and propagation of electrical signals in excitable tissue, it is not very surprising that several isoforms of voltage-activated sodium channels are specifically targeted by many of these venom peptides. Therefore, these peptide toxins provide tremendous opportunities to design drugs with a higher efficacy and fewer undesirable side effects. This review puts venom peptides from spiders, scorpions and cone snails that target voltage-activated sodium channels in the spotlight, and addresses their potential therapeutical applications.
在数百万年的进化过程中，大自然为各种生物提供了大量的毒液库，用于抵御捕食者或捕食猎物。这些毒液是由具有不同功能的多种生物活性化合物组成的丰富混合物，在使受体失去活动能力或杀死受体方面极其有效。事实上，来自各种动物的毒液肽已被证明能特异性作用于离子通道和其他细胞受体，并损害其正常功能。由于它们在可兴奋组织中电信号的起始和传播中起关键作用，许多这些毒液肽特异性靶向电压激活钠通道的几种亚型也就不足为奇了。因此，这些肽毒素为设计疗效更高、不良副作用更少的药物提供了巨大机会。本综述重点介绍了靶向电压激活钠通道的蜘蛛、蝎子和锥螺的毒液肽，并探讨了它们的潜在治疗应用。
