Neurodegeneration and inflammation in Parkinson's disease.
Neurodegeneration and inflammation in Parkinson's disease.
复制标题
DOI：
10.1016/s1353-8020(11)70064-5
复制
发表时间：
2012-01-01
影响因子：
4.1
通讯作者：
Przedborski, Serge
中科院分区：
文献类型：
--
作者：
Phani, Sudarshan;Loike, John D;Przedborski, Serge
帕金森病(PD)的特征是黑质致密部(SNPC)中的多巴胺(DA)神经元进行性变性，并伴有被称为路易小体(Lb)的蛋白质聚集体的积聚。除了蛋白质聚集和DA信号的丢失外，PD还具有主动免疫反应的特点。小胶质细胞和星形胶质细胞在SNPC及其周围活化聚集，伴有T细胞的浸润。虽然小胶质细胞的激活有潜在的好处，但它很可能是通过释放有害物质，如促炎细胞因子、活性氧化物种和活性氮物种，进一步导致疾病病理和DA神经元退化。在小胶质细胞激活相关的COX-2、IL-1β释放和Toll样受体激活后，NF-kappaB死亡通路被激活，导致SNPC的DA神经元变性加剧。在帕金森病动物模型中，阻断小胶质细胞的激活可以导致DA神经元的保护；然而，临床应用抗炎药物并没有产生类似的好处。未来的治疗设计必须考虑帕金森病的多因素性质，包括适应性免疫反应和先天免疫反应的不同作用。
Parkinson's disease (PD) is characterized by the progressive degeneration of dopamine (DA) neurons of the substantia nigra pars compacta (SNpc) accompanied by a buildup of proteinaceous aggregates termed Lewy bodies (LB). In addition to protein aggregation and the loss of DA signaling, PD is also characterized by an active immune response. T-cell infiltration accompanies activated microglial and astrocytic accumulation in and around the SNpc. Although potentially beneficial, microglial activation is most likely responsible for furthering disease pathology and DA neuron degeneration through the release of harmful substances such as pro-inflammatory cytokines, reactive oxidative species and reactive nitrogen species. Activation of the NF-kappaB death pathway has been shown to occur following microglial activation related release of Cox-2, IL-1beta, and Toll-like receptor activation, resulting in increased degeneration of DA neurons of the SNpc. Blockade of microglial activation can lead to DA neuron protection in animal models of PD; however, clinical application of anti-inflammatory drugs has not yielded similar benefits. Future therapeutic designs must take into account the multifactorial nature of PD, including the varied roles of the adaptive and innate immune responses.