摘要
多发性硬化症(multiple sclerosis,MS)是中枢神经系统炎性脱髓鞘疾病,其病理特征为大脑和脊髓多个散在的斑块性神经元轴突髓鞘脱失。MS的发病机制尚未完全阐明,目前认为与病毒感染、自身免疫、遗传和环境等因素有关。CXCR2是一种重要的趋化因子受体,与其配体结合可抑制少突胶质细胞(oligodendrocytes,OLs)的分化、抑制髓鞘再生、介导免疫和炎症反应的作用,在MS发病中发挥重要的作用。抑制CXCR2活性可促进髓鞘的再生和修复,使神经元功能恢复,脱髓鞘症状明显改善。因此,CXCR2可能是治疗MS的重要分子靶点。本文将对CXCR2的功能及其在MS发病中的作用做一综述,为该病的研究和治疗提供新的思路。
Multiple sclerosis is a degenerative inflammatory disease of the CNS,characterized by immune- mediated destruction of myelin and progressive neuroaxonal loss.The pathogenesis of MS has not been fully elucidated and is currently considered to be related to viral infections,autoimmunity,genetics,and environmental factors. Therefore,a regenerative strategy to promote remyelination may protect axons and improve symptoms of multiple sclerosis.Although immunomodulatory therapies are being proven to be effective in controlling the initial symptom of MS,the continual atrophy of demyelinated axons remains largely untreatable.Several regulators of remyelination have been identified as potential therapeutic targets to induce remyelination,of which CXCR2is an important one. CXCR2is a powerful neutrophil chemotactic factor and first found as interteukin-8receptor.CXCR2is involved in the immune response and inflammatory response in the process of MS and facilitates inflammatory demyelination. CXCR2antagonists at the onset of MS decrease demyelinated lesions and promote myelin regeneration,therefore restore neuronal function.Thus,CXCR2might be a promising drug target for clinical demyelinating disorders as it contributes to both the inflammatory and remyelination processes.In this review we summarized the functions of CXCR2.In particular,we discussed the role of CXCR2in the pathogenesis of MS by reviewing many studies that targeted CXCR2as novel therapeutic approach,thus to provide theoretical basis for the treatment of MS.
作者
王璐
杨瀚宇
臧彩霞
鲍秀琦
张丹
WANG Lu;YANG Han-yu;ZANG Cai-xia;BAO Xiu-qi;ZHANG Dan(State Key Laboratory of Natural Products and Functions,Institute of Materia Medica,Chinese Academy of Medical Sciences &Peking Union Medical College,Beijing 100050,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2018年第22期2630-2635,共6页
Chinese Journal of New Drugs
基金
国家自然科学基金资助项目(81630097,81773718)
中国医学科学院医学与健康科技创新工程资助项目(2016-12M-3-011)
