期刊
NEURAL REGENERATION RESEARCH
卷 17, 期 8, 页码 1841-1849出版社
WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.4103/1673-5374.332160
关键词
Alzheimer's disease; cognitive function; complement system; CR1; Crry; neurodegeneration; neuroinflammation; tauopathy
资金
- National Natural Science Foundation of China [81801054]
- Natural Science Foundation of Jiangsu Province of China [BK20180166]
- Wuxi Municipal Health and Family Planning Commission Fund of China [Q201722]
- Wuxi Top Talent Support Program for Young and Middle-aged People of Wuxi Health Committee of China [HB2020023]
- China Postdoctoral Funding
CR1 is involved in the phosphorylation of tau protein and its silencing reduces tau phosphorylation and improves cognitive function by regulating neuroinflammation and complement component levels.
Complement component (3b/4b) receptor 1 (CR1) expression is positively related to the abundance of phosphorylated microtubuleassociated protein tau (tau), and CR1 expression is associated with susceptibility to Alzheimer's disease. However, the exact role of CR1 in tau protein-associated neurodegenerative diseases is unknown. In this study, we show that the mouse Cr1-related protein Y (Crry) gene, Crry, is localized to microglia. We also found that Crry protein expression in the hippocampus and cortex was significantly elevated in P301S mice (a mouse model widely used for investigating tau pathology) compared with that in wild-type mice. Tau protein phosphorylation (at serine 202, threonine 205, threonine 231, and serine 262) and expression of the major tau kinases glycogen synthase kinase-3 beta and cyclindependent-like kinase 5 were greater in P301S mice than in wild-type mice. Crry silencing by lentivirus-transfected short hairpin RNA led to greatly reduced tau phosphorylation and glycogen synthase kinase-3 beta and cyclin-dependent-like kinase 5 activity. Crry silencing reduced neuronal apoptosis and rescued cognitive impairment of P301S mice. Crry silencing also reduced the levels of the neuroinflammatory factors interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 and the complement components complement 3 and complement component 3b. Our results suggest that Crry silencing in the P301S mouse model reduces tau protein phosphorylation by reducing the levels of neuroinflammation and complement components, thereby improving cognitive function.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据