吞噬作用
炎症
巨噬细胞
生物
免疫系统
小胶质细胞
神经退行性变
流式细胞术
基因敲除
细胞生物学
细胞凋亡
免疫学
表型
体外
医学
病理
疾病
遗传学
基因
作者
Dhanya Krishnan,Ramshekhar N. Menon,Mathuranath PS,Srinivas Gopala
出处
期刊:
[Cold Spring Harbor Laboratory]
日期:2019-08-19
摘要
Abstract INTRODUCTION Defective immune cell-mediated clearance of amyloid-beta (Aβ) and Aβ-associated inflammatory activation of immune cells are key contributors of Aβ accumulation and neurodegeneration in Alzheimer’s disease (AD), however, the underlying mechanisms remain elusive. METHODS Differentiated THP-1 cells treated with Aβ and AD patient-derived macrophages were used as in-vitro model. The role of SHARPIN was analysed in differentiated THP-1 cells using siRNA-mediated knockdown followed by immunoblotting, ELISA, real-time PCR, immunoprecipitation and flow cytometry. Differentiated SHSY5Y cells were used to study inflammation-mediated apoptosis. RESULTS SHARPIN was found to regulate Aβ-phagocytosis and NLRP3 expression in THP-1 derived macrophages. Further, it was found to promote macrophage polarization to an M1 (pro-inflammatory) phenotype resulting in enhanced inflammation and associated neuronal death, demonstrated using in-vitro culture systems. SHARPIN expression by blood-derived macrophages was further found to be higher in the early stages of AD, which correlates with Aβ 40/42 concentration in the plasma and age of the study subjects. DISCUSSION The novel protein, SHARPIN has been shown to play critical roles in regulation of Aβ-phagocytosis and inflammation in AD and the mechanism by which SHARPIN is activated by Aβ in macrophages has been elucidated.
科研通智能强力驱动
Strongly Powered by AbleSci AI