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| Activated Scavenger Receptor A Promotes Glial Internalization of A beta | |
| Alternative Title | PLoS 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 Publication | PLOS ONE
 |
| ISSN | 1932-6203 |
| Volume | 9Issue:4Pages:11 |
| Abstract | 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.; 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. |
| Keyword | Alzheimers-disease Amyloid-beta Microglial Activation Neuronal Viability Signaling Pathways Transgenic Mice Peptide Phagocytosis Clearance Cells |
| Subtype | Article |
| WOS Headings | Science & Technology |
| DOI | 10.1371/journal.pone.0094197 |
| URL | 查看原文 |
| Indexed By | SCI |
| Language | 英语 |
| WOS Keyword | ALZHEIMERS-DISEASE ; AMYLOID-BETA ; MICROGLIAL ACTIVATION ; NEURONAL VIABILITY ; SIGNALING PATHWAYS ; TRANSGENIC MICE ; PEPTIDE ; PHAGOCYTOSIS ; CLEARANCE ; CELLS |
| WOS Research Area | Science & Technology - Other Topics |
| WOS Subject | Multidisciplinary Sciences |
| WOS ID | WOS:000334339000087 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Version | 出版稿 |
| Identifier | http://ir.ipe.ac.cn/handle/122111/11027 |
| Collection | 研究所（批量导入） |
| Affiliation | 1.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. |
| Files in This Item: | ||||||
| File Name/Size | DocType | Version | Access | License | ||
| Activated Scavenger （1147KB） | 限制开放 | CC BY-NC-SA | Application Full Text | |||
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