賀中國科學(xué)院工程研究所和清華大學(xué)生命科學(xué)學(xué)院應(yīng)用PriCells產(chǎn)品/技術(shù)服務(wù)發(fā)表文章
Activated Scavenger Receptor A Promotes Glial Internalization of Ab
PLOS ONE Published: April 09,2014 DOI:10.1371/journal.pone.0094197
He Zhang1,2, Ya-jing Su3, Wei-wei Zhou1, Shao-wei Wang1, Peng-xin Xu1, Xiao-lin Yu1*, Rui-tian Liu1*
1 National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China,
2 Tsinghua University School of Medicine, Haidian District, Beijing, China,
3 School of Life Science, Ningxia University, Yinchuan, China
Abstract
Beta-amyloid (Aβ) aggregates have a pivotal role in pathological processing of Alzheimer’s disease (AD). The clearance of Aβ monomer or aggregates is a causal strategy for AD treatment. Microglia and astrocytes are the main macrophages that exert critical neuroprotective roles in the brain. They may effectively clear the toxic accumulation of Aβ at the initial stage of AD, however, their functions are attenuated because of glial overactivation. In this study, we first showed that heptapeptide XD4 activates the class A scavenger receptor (SR-A) on the glia by increasing the binding of Aβ to SR-A, thereby promoting glial phagocytosis of Aβ oligomer in microglia and astrocytes and triggering intracellular mitogen-activated protein kinase (MAPK) signaling cascades. Moreover, XD4 enhances the internalization of Aβ monomers to microglia and astrocytes through macropinocytosis or SR-A-mediated phagocytosis. Furthermore, XD4 significantly inhibits Aβ oligomer-induced cytotoxicity to glial cells and decreases the production of proinflammatory cytokines, such as TNF-α and IL-1β, in vitro and in vivo. Our findings may provide a novel strategy for AD treatment by activating SR-A.
MIC-CELL-0077 / MED-0014，PriCells
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