Microglial Activation in the Pathogenesis of Huntington's Disease.
Microglial Activation in the Pathogenesis of Huntington's Disease.
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小胶质细胞激活在亨廷顿病发病机制中的作用
DOI：
10.3389/fnagi.2017.00193
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发表时间：
2017
影响因子：
4.8
通讯作者：
Guo JF
中科院分区：
文献类型：
--
作者：
Yang HM;Yang S;Huang SS;Tang BS;Guo JF
亨廷顿氏病（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HTT基因1外显子CAG三核苷酸重复（bbb36）扩增引起。虽然HD的特点是纹状体和皮层神经元的主要损失，但先前的研究指出，突变亨廷顿蛋白在小胶质细胞中的异常积累，通过细胞自主和非细胞自主机制，有助于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视微环境。在各种促炎刺激下，小胶质细胞被激活并经历两个不同的阶段（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）。小胶质细胞激活的免疫调节可能具有神经毒性，也可能具有神经保护作用。在这篇综述中，我们总结了目前关于小胶质细胞激活在HD发病和进展中的认识，主要关注激活的小胶质细胞M1和M2表型及其相应的信号通路。
Huntington’s disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by expanded CAG trinucleotide repeats (>36) in exon 1 of HTT 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.