基于Keap1-Nrf2-ARE信号通路对多发性硬化症治疗的研究及展望

Research and Prospect of Treatment of MS Based on Keap1-Nrf2-ARE Signaling Pathway

多发性硬化症(multiple sclerosis,MS)是一种炎症性神经退行性疾病,已被列入《中国第一批罕见病目录》。目前研究的药物只能缓解MS病程,但仍不能彻底治愈。激活核因子E2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)能够有效缓解MS的复发和临床症状。Kelch样环氧氯丙烷相关蛋白-1(epoxy chloropropane Kelch sample related protein-1,Keap1)-Nrf2蛋白相互作用抑制剂有别于亲电性Nrf2激活剂,避免了脱靶毒性效应,是激活Nrf2的新方式。激活Nrf2对MS患者及动物模型中的免疫炎性反应、铁代谢、自噬等生理过程有一定程度的影响。本文分析并总结了Nrf2激活剂以及激活Nrf2途径与MS的相互联系。

Multiple sclerosis(MS)is an inflammatory neurodegenerative disease that has been included in the"First Catalog of Rare Diseases in China".The drugs currently studied can only relieve the course of MS,but MS still cannot be completely cured.Activating nuclear factor erythroid 2-related factor 2(Nrf2)can effectively relieve the recurrence of MS and clinical symptoms.Activation of Nrf2 via Inhibition of Kelch-like epichlorohydrin-related protein-1(Keap1)-Nrf2 protein interaction is preferred than electrophilic Nrf2 activators,which avoids off-target toxic effects,and works as a new approach to activate Nrf2.Related studies have shown that the activation of Nrf2 has a certain degree of influence on the immune inflammation,iron metabolism,and autophagy in MS patients and animal models.This article summarizes the Nrf2 activator and the interaction between the Nrf2 pathway and MS.