Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK.
Department of Neurology, The First People's Hospital of Yunnan Province, Kunming 650032, China.
Genes (Basel). 2021 Oct 30;12(11):1753. doi: 10.3390/genes12111753.
Neuroinflammatory mechanisms with glial cell activation have been implicated in the pathogenic process of Alzheimer's disease (AD). Activation of the NLRP3 inflammasome is an essential component of the neuroinflammatory response. A role for NLRP3 activation in AD is supported by both in vitro and in vivo preclinical studies with little direct investigation of AD brain tissue. RNA expression of genes of three glial cell markers, HLA-DRA, AIF-1 and GFAP; the components of the NLRP3 inflammasome NLRP3, ASC, and caspase-1; and downstream pre-inflammatory cytokines IL-1 β and IL-18, were investigated in the temporal cortex of AD patients and age- and sex-matched controls. Protein expression of GFAP was also assessed. Increases in both mRNA and protein expression were observed for GFAP in AD. There were no significant changes in other NLRP3 activation markers between groups. Our results indicate the involvement of astrocyte activation in AD, particularly in more severe patients. We found no evidence for the specific involvement of the NLRP3 inflammasome.
神经炎症机制和神经胶质细胞激活被认为与阿尔茨海默病（AD）的发病机制有关。NLRP3 炎性小体的激活是神经炎症反应的一个重要组成部分。体外和体内临床前研究都支持 NLRP3 激活在 AD 中的作用，但对 AD 脑组织的直接研究很少。研究人员调查了 AD 患者和年龄、性别匹配的对照组颞叶皮层中三种神经胶质细胞标志物 HLA-DRA、AIF-1 和 GFAP 的基因、NLRP3 炎性小体 NLRP3、ASC 和半胱天冬酶-1 的组成部分以及下游前炎症细胞因子 IL-1β 和 IL-18 的 RNA 表达。还评估了 GFAP 的蛋白表达。AD 患者的 GFAP 无论是在 mRNA 还是蛋白表达上均增加。各组之间其他 NLRP3 激活标志物没有明显变化。我们的研究结果表明星形胶质细胞激活参与了 AD，特别是在更严重的患者中。我们没有发现 NLRP3 炎性小体的具体参与证据。
