Small molecule neurolysin activators, potential multi-mechanism agents for ischemic stroke therapy.
Small molecule neurolysin activators, potential multi-mechanism agents for ischemic stroke therapy.
复制标题
小分子溶神经素激活剂，缺血性中风治疗的潜在多机制药物。
DOI：
10.1080/14728222.2022.2077190
复制
发表时间：
2022
影响因子：
5.8
通讯作者：
Karamyan,VardanT
中科院分区：
文献类型：
--
作者：
Esfahani,ShivaHadi;Abbruscato,ThomasJ;Trippier,PaulC;Karamyan,VardanT
正如我们经常从自然界中了解到的那样，阐明和理解大脑的内源性自我保护和恢复机制已经成为中风研究领域的一种新兴方法，以满足开发新疗法的未满足需求[1]。对于急性缺血性卒中，其构成涉及兴奋性毒性、氧化应激、血脑屏障（BBB）高通透性、神经炎症、水肿形成和细胞死亡的多因素病理过程，该方法的基本前提是模仿或参与大脑的自我保护机制可以提供脑保护和有效的卒中治疗。我们小组确定的一种此类机制是肽酶神经溶解素（Nln），其被视为卒中后大脑中的代偿性和保护性酶，并且正在研究其作为急性缺血性卒中治疗的潜在药物靶点[2]。这篇集中的观点文章简要讨论了Nln及其肽底物在缺血性脑中的多方面功能，并详细介绍了小分子Nln激活剂作为治疗急性缺血性卒中的潜在新型多机制药物的开发进展。
As we often learn from nature, elucidation and understanding of the brain’s endogenous self-protective and recovery mechanisms have been an emerging approach in the stroke research field to fulfill the unmet need for development of new therapies [1]. For acute ischemic stroke, which constitutes a multifactorial pathological process involving excitotoxicity, oxidative stress, blood–brain barrier (BBB) hyperpermeability, neuroinflammation, edema formation, and cell death, the basic premise of this approach is that mimicking or engaging the brain’s self-protective mechanisms could afford cerebroprotection and effective stroke therapy. One such mechanism identified by our group is peptidase neurolysin (Nln), which is viewed as a compensatory and cerebroprotective enzyme in the post-stroke brain and is being investigated as a potential drug target for acute, ischemic stroke therapy [2]. This focused opinion paper briefly discusses the multi-faceted function of Nln and its peptide substrates in the ischemic brain and details the progress made in development of small molecule Nln activators as a potential new class of multi-mechanism agents for the treatment of acute ischemic stroke.