Inflammasomes in neurological diseases: emerging pathogenic and therapeutic concepts
Inflammasomes in neurological diseases: emerging pathogenic and therapeutic concepts
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DOI：
10.1093/brain/awx133
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发表时间：
2017-09-01
期刊：
影响因子：
14.5
通讯作者：
Power, Christopher
中科院分区：
文献类型：
--
作者：
Mamik, Manmeet K.;Power, Christopher
中枢神经系统中的炎性小体激活在健康和疾病中都存在。炎性小体是一种胞浆蛋白复合体，它能感知特定的感染或宿主刺激，并通过激活caspase来启动炎症反应。炎性小体的组装导致caspase-1介导的蛋白分解和促炎细胞因子IL-1β和IL-18的释放，从而引发下垂，一种炎性程序性细胞死亡。炎症体领域的最新进展揭示了导致一系列神经系统疾病的新的分子机制，包括与炎症体基因的特定突变相关的疾病以及由炎症体激活调节的疾病。这一最新进展集中在炎症体生物学领域的最新发展，突出不同的炎症体激活剂和在神经系统中发现的途径。我们还讨论了调节炎症小体和改善神经预后的靶向治疗。
Inflammasome activation in the central nervous system occurs in both health and disease. Inflammasomes are cytosolic protein complexes that sense specific infectious or host stimuli and initiate inflammatory responses through caspase activation. Assembly of inflammasomes results in caspase-1-mediated proteolytic cleavage and release of the pro-inflammatory cytokines, interleukin-1 beta and interleukin-18, with initiation of pyroptosis, an inflammatory programmed cell death. Recent developments in the inflammasome field have uncovered novel molecular mechanisms that contribute to a broad range of neurological disorders including those associated with specific mutations in inflammasome genes as well as diseases modulated by inflammasome activation. This update focuses on recent developments in the field of inflammasome biology highlighting different inflammasome activators and pathways discovered in the nervous system. We also discuss targeted therapies that regulate inflammasomes and improve neurological outcomes.