Salman Mohd, Parvez Suhel
Department of Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110 062, India.
Department of Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110 062, India; Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN, USA.
Life Sci. 2023 Mar 15;317:121365. doi: 10.1016/j.lfs.2022.121365. Epub 2023 Jan 11.
Globally, Ischemic stroke (IS) has become the second leading cause of mortality and chronic disability. The process of IS has triggered by the blockages of blood vessels to form clots in the brain which initiates multiple interactions with the key signaling pathways, counting excitotoxicity, acidosis, ionic imbalance, inflammation, oxidative stress, and neuronal dysfunction of cells, and ultimately cells going under apoptosis. Currently, FDA has approved only tissue plasminogen activator therapy, which is effective against IS with few limitations. However, the mechanism of excitotoxicity and acidosis has spurred the investigation of a potential candidate for IS therapy. Acid-sensing ion channels (ASICs) and Voltage-gated Ca channels (VDCCs) get activated and disturb the brain's normal physiology. Animal toxins are novel inhibitors of ASICs and VDCCs channels and have provided neuroprotective insights into the pathophysiology of IS. This review will discuss the potential directions of translational ASICs and VDCCs inhibitors research for clinical therapies.
在全球范围内，缺血性中风（IS）已成为第二大致死和慢性残疾原因。IS的发病过程是由血管阻塞在大脑中形成血栓引发的，这会引发与关键信号通路的多种相互作用，包括兴奋性毒性、酸中毒、离子失衡、炎症、氧化应激以及细胞的神经元功能障碍，最终导致细胞凋亡。目前，美国食品药品监督管理局（FDA）仅批准了组织纤溶酶原激活剂疗法，该疗法对IS有效，但有一些局限性。然而，兴奋性毒性和酸中毒的机制促使人们对IS治疗的潜在候选药物进行研究。酸敏感离子通道（ASICs）和电压门控钙通道（VDCCs）被激活并扰乱大脑的正常生理功能。动物毒素是ASICs和VDCCs通道的新型抑制剂，并为IS的病理生理学提供了神经保护方面的见解。本综述将讨论转化型ASICs和VDCCs抑制剂用于临床治疗研究的潜在方向。
