贺中国科学院工程研究所和清华大学生命科学学院应用PriCells产品/技术服务发表文章

 

Activated Scavenger Receptor A Promotes Glial Internalization of Ab

 

PLOS ONE Published: April 09,2014 DOI:10.1371/journal.pone.0094197

 

He Zhang^1,2, Ya-jing Su³, Wei-wei Zhou¹, Shao-wei Wang¹, Peng-xin Xu¹, Xiao-lin Yu^1*, Rui-tian Liu^1*

 

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