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Activated Scavenger Receptor A Promotes Glial Internalization of A beta
Alternative TitlePLoS One
Zhang, He1,2; Su, Ya-jing3; Zhou, Wei-wei1; Wang, Shao-wei1; Xu, Peng-xin1; Yu, Xiao-lin1; Liu, Rui-tian1
2014-04-09
Source PublicationPLOS ONE
ISSN1932-6203
Volume9Issue:4Pages:11
AbstractBeta-amyloid (Ab) aggregates have a pivotal role in pathological processing of Alzheimer's disease (AD). The clearance of Ab 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 Ab 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 Ab to SR-A, thereby promoting glial phagocytosis of Ab oligomer in microglia and astrocytes and triggering intracellular mitogen-activated protein kinase (MAPK) signaling cascades. Moreover, XD4 enhances the internalization of A beta monomers to microglia and astrocytes through macropinocytosis or SR-A-mediated phagocytosis. Furthermore, XD4 significantly inhibits A beta oligomer-induced cytotoxicity to glial cells and decreases the production of proinflammatory cytokines, such as TNF-alpha and IL-1 beta, in vitro and in vivo. Our findings may provide a novel strategy for AD treatment by activating SR-A.; Beta-amyloid (Ab) aggregates have a pivotal role in pathological processing of Alzheimer's disease (AD). The clearance of Ab 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 Ab 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 Ab to SR-A, thereby promoting glial phagocytosis of Ab oligomer in microglia and astrocytes and triggering intracellular mitogen-activated protein kinase (MAPK) signaling cascades. Moreover, XD4 enhances the internalization of A beta monomers to microglia and astrocytes through macropinocytosis or SR-A-mediated phagocytosis. Furthermore, XD4 significantly inhibits A beta oligomer-induced cytotoxicity to glial cells and decreases the production of proinflammatory cytokines, such as TNF-alpha and IL-1 beta, in vitro and in vivo. Our findings may provide a novel strategy for AD treatment by activating SR-A.
KeywordAlzheimers-disease Amyloid-beta Microglial Activation Neuronal Viability Signaling Pathways Transgenic Mice Peptide Phagocytosis Clearance Cells
SubtypeArticle
WOS HeadingsScience & Technology
DOI10.1371/journal.pone.0094197
URL查看原文
Indexed BySCI
Language英语
WOS KeywordALZHEIMERS-DISEASE ; AMYLOID-BETA ; MICROGLIAL ACTIVATION ; NEURONAL VIABILITY ; SIGNALING PATHWAYS ; TRANSGENIC MICE ; PEPTIDE ; PHAGOCYTOSIS ; CLEARANCE ; CELLS
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000334339000087
Citation statistics
Cited Times:20[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Version出版稿
Identifierhttp://ir.ipe.ac.cn/handle/122111/11027
Collection研究所(批量导入)
Affiliation1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing, Peoples R China
2.Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China
3.Ningxia Univ, Sch Life Sci, Yinchuan, Peoples R China
Recommended Citation
GB/T 7714
Zhang, He,Su, Ya-jing,Zhou, Wei-wei,et al. Activated Scavenger Receptor A Promotes Glial Internalization of A beta[J]. PLOS ONE,2014,9(4):11.
APA Zhang, He.,Su, Ya-jing.,Zhou, Wei-wei.,Wang, Shao-wei.,Xu, Peng-xin.,...&Liu, Rui-tian.(2014).Activated Scavenger Receptor A Promotes Glial Internalization of A beta.PLOS ONE,9(4),11.
MLA Zhang, He,et al."Activated Scavenger Receptor A Promotes Glial Internalization of A beta".PLOS ONE 9.4(2014):11.
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