CKLF1作为缺血性脑卒中治疗的潜在靶点

CKLF1 as a Potential Therapeutic Target for Ischemic Stroke

缺血性脑卒中是一种血液循环障碍疾病,可导致严重的神经功能缺损。卒中病人中约有87%的病例为缺血性卒中。神经炎症是中风损伤的主要病理状态之一。CKLF1是2001年发现的非经典CC型趋化因子,对单核细胞、中性粒细胞和淋巴细胞表现出很强的趋化活性。CKLF1在胎儿大脑中含量最高,但在健康成人阶段不存在。越来越多的证据表明,CKLF1表达在成年卒中动物模型中,并被重新激活,参与神经炎症反应的多个过程。然而,其生物活性和药物发现的发展仍缺乏系统的文献报道。因此,我们收集已发表的资料并做此综述,简要阐明CKLF1在缺血性脑卒中中的作用,并解释其加重缺血性脑卒中的机制。此外,还发现了一些潜在的抗卒中药物,表明CKLF1是治疗缺血性卒中的潜在靶点。

Ischemic stroke is a kind of stroke in which the blood supply to the brain is disrupted,resulting in serious neurological deficits.Among stroke patients,about 87%of the cases are ischemic stroke.Neuroinflammation is one of the main pathological conditions of stroke injury.CKLF1 is a non-classical CC-type chemokine discovered in 2001,which showed strong chemotactic activity on monocytes,neutrophils,and lymphocytes.CKLF1 is most abundant in the fetal brain,but absent in the healthy adult.Growing evidence shows that CKLF1 is reactivated and expressed in adult stroke animal models and participates in multiple processing of neuroinflammatory responses.CKLF1 could activate the polarization of microglia to produce inflammatory mediators and trigger inflammation in the injured brain.And then they drove peripheral immune cells such as neutrophils to recruit into the injured brain.These stimulated the greater immune responses and destroyed the fragile blood-brain barrier(BBB).We believe that CKLF1 plays an important role in the course of ischemic stroke.However,the development of its biological activity and drug discovery lacks systematic literature reports.Thus,we collected the published data and made this review,to briefly describe the role of CKLF1 in ischemic stroke,and explained its mechanism of aggravating ischemic stroke.Moreover,some potential anti-stroke drugs have been discovered,indicating that CKLF1 is a potential target for the treatment of ischemic stroke.