小胶质细胞异常激活在帕金森病发病中的作用及潜在临床应用

The role of abnormally activated microglia in the pathogenesis of Parkinson's disease and its potential clinical application

帕金森病为老年人群中常见的神经系统变性疾病,发病机制至今不明。近年研究表明,异常激活的小胶质细胞在神经炎症机制介导的帕金森病发病过程中起重要作用,小胶质细胞可在α突触共核蛋白、环境毒素、老龄化等因素的刺激下,以及内源性CD200-CD200R抑制信号减弱或缺失的情况下发生异常激活,通过分泌大量炎性因子(如肿瘤坏死因子α、IL1β等)活化诱导型一氧化氮合酶、环氧合酶2、烟酰胺腺嘌呤二核苷酸磷酸氧化酶2等介导神经元损伤。抑制小胶质细胞异常激活从而有效抑制免疫炎性损伤,可能是帕金森病治疗的有效新途径。

Parkinson＇s disease （PD） is a neurodegenerative disorder which usually affects old-aged people, and the mechanism underling the disease still remains unknown. Recent studies have suggested that abnormally activated microglia plays an important role in the pathogenesis of the disease. Several stimuli, such as ct-synuclein, neurotoxins, aging, as well as attenuated or deficient inhibiting signals of endogenous CD200- CD200R can cause the abnormal activation of microglia, which will result in dopaminergic neuron injuries through secreting pro-inflammatory cytokines such as tumor necrosis factor-ct （TNF-o） and interleukin-1 （IL-1 ）, activating inducible nitric oxide synthase （iNOS）, cyclooxygenase-2 （COX-2） and nicotinamide adenine dinucleotide phosphate oxidase-2 （NOX-2）. Therefore, it may be a novel way for PD therapy to inhibit neuroinflammatory injuries by suppressing the abnormal activation of microglia.