外周炎症和中枢炎症在帕金森病发病机制中的作用

The Role of Central and Peripheral Infammation in the Pathogenesis of Parkinson's Disease

帕金森病(PD)是第二常见的神经退行性疾病,主要临床症状为运动障碍,给患者带来极大困扰。近年来大量研究表明,PD与外周和中枢炎症密切相关。PD患者首先出现便秘等运动前症状,肠道屏障功能障碍和肠道微生物失调加速肠神经胶质细胞激活、α-突触核蛋白聚集以及外周免疫细胞增殖,产生各种促炎细胞因子和趋化因子。大脑内,各种病原体相关分子模式(PAMPs)和组织相关分子模式(DAMPs)激活小胶质细胞,主要通过TLRSNF-κB-NLRP3信号通路促进NLRP3炎性小体组装,促炎因子释放,最终导致多巴胺能神经元死亡。外周促炎因子使血脑屏障通透性增加,淋巴细胞、单核/巨噬细胞等外周免疫细胞进一步加剧中枢神经炎症。文中总结了外周炎症和中枢炎症在PD发病中的作用,为今后治疗PD提供可能的治疗靶点。

T Parkinson's disease(PD)is the second common neurodegenerative disease.The main clinical symptom is movement disorder,which brings great trouble to patients.In recent years,a large number of studies have shown that PD is closely related to peripheral and central inflammation.Firstly,PD patients show pre-exercise symptoms such as constipation.Intestinal barrier dysfunction and intestinal microbial imbalance can accelerate the activation of intestinal glial cells,α-synuclein(α-syn)aggregation and peripheral immune cell proliferation,then producing various proinflammatory cytokines and chemokines.In the brain,various pathogen related molecular patterns(PAMPs)and tissue related molecular patterns(DAMPs)activate microglia,promoting the assembly of NLRP3 inflammasome and the release of proinflammatory factors through TLRs-NF-kb-NLRP3 pathway,and finally leading to the death of dopaminergic neurons.Proinflammatory factors increase the permeability of blood-brain barrier(BBB),and peripheral immune cells such as lymphocytes and monocytes/macrophages further aggravate the central nervous inflammation.The role of central inflammation and peripheral inflammation in the pathogenesis of PD was reviewed,so as to provide possible therapeutic targets for the treatment of PD in the future.