Yang Hui-Ming, Yang Su, Huang Shan-Shan, Tang Bei-Sha, Guo Ji-Feng
Department of Neurology, Xiangya Hospital, Central South UniversityChangsha, China.
Department of Human Genetics, Emory University School of Medicine, AtlantaGA, United States.
Front Aging Neurosci. 2017 Jun 19;9:193. doi: 10.3389/fnagi.2017.00193. eCollection 2017.
Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by expanded CAG trinucleotide repeats (>36) in exon 1 of gene that encodes huntingtin protein. Although HD is characterized by a predominant loss of neurons in the striatum and cortex, previous studies point to a critical role of aberrant accumulation of mutant huntingtin in microglia that contributes to the progressive neurodegeneration in HD, through both cell-autonomous and non-cell-autonomous mechanisms. Microglia are resident immune cells in the central nervous system (CNS), which function to surveil the microenvironment at a quiescent state. In response to various pro-inflammatory stimuli, microglia become activated and undergo two separate phases (M1 and M2 phenotype), which release pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), anti-inflammatory cytokines, and growth factors (TGF-β, CD206, and Arg1), respectively. Immunoregulation by microglial activation could be either neurotoxic or neuroprotective. In this review, we summarized current understanding about microglial activation in the pathogenesis and progression of HD, with a primary focus of M1 and M2 phenotype of activated microglia and their corresponding signaling pathways.
亨廷顿舞蹈症（HD）是一种常染色体显性遗传的神经退行性疾病，由编码亨廷顿蛋白的基因外显子1中CAG三核苷酸重复序列扩增（>36）引起。尽管HD的特征是纹状体和皮质中神经元大量丧失，但先前的研究指出，突变型亨廷顿蛋白在小胶质细胞中异常积累起着关键作用，通过细胞自主和非细胞自主机制导致HD的进行性神经退行性变。小胶质细胞是中枢神经系统（CNS）中的常驻免疫细胞，其功能是在静止状态下监测微环境。响应各种促炎刺激，小胶质细胞被激活并经历两个不同阶段（M1和M2表型），分别释放促炎细胞因子（IL-1β、IL-6和TNF-α）、抗炎细胞因子和生长因子（TGF-β、CD206和Arg1）。小胶质细胞激活介导的免疫调节可能具有神经毒性或神经保护作用。在本综述中，我们总结了目前对HD发病机制和进展过程中小胶质细胞激活的认识，主要关注激活的小胶质细胞的M1和M2表型及其相应的信号通路。
