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NLRP3 炎性小体抑制剂在抗癫痫药物发现和开发中的应用。

NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development.

机构信息

Research and Development Service, Kansas City Veterans Affairs Medical Center, Kansas City, MO 64128, USA.

Department of Math, Science and Business Technology, Kansas City Kansas Community College, Kansas City, KS 66112, USA.

出版信息

Int J Mol Sci. 2024 May 31;25(11):6078. doi: 10.3390/ijms25116078.

DOI:10.3390/ijms25116078
PMID:38892264
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11172514/
Abstract

Epilepsy is one of the most prevalent and serious brain disorders and affects over 70 million people globally. Antiseizure medications (ASMs) relieve symptoms and prevent the occurrence of future seizures in epileptic patients but have a limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms of these medications for the development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made, and challenges faced in the development of NLRP3 inhibitors for the treatment of epilepsy.

摘要

癫痫是最常见和最严重的脑部疾病之一，影响着全球超过 7000 万人。抗癫痫药物（ASM）可缓解症状并预防癫痫患者未来的癫痫发作，但对癫痫发生的影响有限。要解决癫痫发生的多方面性质及其与 Nod 样受体家族 pyrin 结构域包含 3（NLRP3）炎性小体介导的神经炎症的关联，需要全面了解这些药物的潜在机制，以便开发针对传统抗癫痫治疗的靶向治疗策略。已经开发了几种类型的 NLRP3 抑制剂，并且已经在癫痫发生的体外和体内模型中验证了它们的效果。在这篇综述中，我们讨论了理解 NLRP3 激活的调节机制的进展，以及在开发用于治疗癫痫的 NLRP3 抑制剂方面取得的进展和面临的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/11172514/811eb605a39b/ijms-25-06078-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/11172514/60ff844602b3/ijms-25-06078-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/11172514/34eae54b43ef/ijms-25-06078-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/11172514/811eb605a39b/ijms-25-06078-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/11172514/60ff844602b3/ijms-25-06078-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/11172514/34eae54b43ef/ijms-25-06078-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/11172514/811eb605a39b/ijms-25-06078-g003.jpg

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