钙离子通道调节剂在神经元的生长锥的作用及临床意义（英文）

Effects of calcium channel blockers on growth cone and their clinical implications

钙是神经发育过程中重要的信号分子,其生物学功能通过众多的钙离子通道、交换蛋白及钙结合蛋白来实现。在神经发育过程中,神经元的生长锥利用钙离子的浓度差来进行正确爬行,并最终引导轴突向正确的方向生长。然而,如果钙离子通道出现功能障碍,将会引起生长锥错误地爬行,从而导致神经发育相关疾病的发生。了解特异性表达于生长锥的钙通道,并获得能调控这些钙通道的调节剂对于治疗神经发育相关疾病至关重要。这些调节剂可能已广泛用于其他组织病变,如心血管疾病的治疗。但它们对生长锥上钙通道的调控仍有待进一步研究。最近的研究表明,离子通道调节剂可以作为治疗神经发育相关疾病的药物靶标。本文讨论钙通道调节剂在生长锥引导轴突生长过程中的潜在作用。

Calcium signaling is a critical component of neuronal development, and is mediated by numerous calcium channels, exchangers and calcium-binding proteins. Growth cones use calcium gradient as a tool to pathfind correctly, ultimately directing the appropriate growth of axons. Conse- quently, dysfunctions of calcium channels could lead to incorrect pathfinding, thus resulting in develop- mental disorders. It is important to understand the pharmacological modulators of the calcium channels present in the growth cone-some already widely used in other tissue pathologies, like cardiovascular disease. Further, L-type channel blockers such as dihydropyridines have been instrumental in under- standing the properties of L-type channels as well as their heterogeneous nature. Investigation of channel property often uses pharmacological inhibition to reveal their functionality. Recent studies show the channel modulators as promising drug targets in the treatment of neurodevelopmental disorders. The goal of this article is to discuss the potential effects of pharmacological regulators of growth cone calcium channels on outgrowth activity.