Activated Scavenger Receptor A Promotes Glial Internalization of Aβ

Activated Scavenger Receptor A Promotes Glial Internalization of Aβ

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...

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Main Authors: Zhang, He, Su, Ya-jing, Zhou, Wei-wei, Wang, Shao-wei, Xu, Peng-xin, Yu, Xiao-lin, Liu, Rui-tian
Format: Online
Language:English
Published: Public Library of Science 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981768/
id pubmed-3981768
recordtype oai_dc
spelling pubmed-39817682014-04-11 Activated Scavenger Receptor A Promotes Glial Internalization of Aβ Zhang, He Su, Ya-jing Zhou, Wei-wei Wang, Shao-wei Xu, Peng-xin Yu, Xiao-lin Liu, Rui-tian Research Article 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. Public Library of Science 2014-04-09 /pmc/articles/PMC3981768/ /pubmed/24718459 http://dx.doi.org/10.1371/journal.pone.0094197 Text en © 2014 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Zhang, He
Su, Ya-jing
Zhou, Wei-wei
Wang, Shao-wei
Xu, Peng-xin
Yu, Xiao-lin
Liu, Rui-tian
spellingShingle Zhang, He
Su, Ya-jing
Zhou, Wei-wei
Wang, Shao-wei
Xu, Peng-xin
Yu, Xiao-lin
Liu, Rui-tian
Activated Scavenger Receptor A Promotes Glial Internalization of Aβ
author_facet Zhang, He
Su, Ya-jing
Zhou, Wei-wei
Wang, Shao-wei
Xu, Peng-xin
Yu, Xiao-lin
Liu, Rui-tian
author_sort Zhang, He
title Activated Scavenger Receptor A Promotes Glial Internalization of Aβ
title_short Activated Scavenger Receptor A Promotes Glial Internalization of Aβ
title_full Activated Scavenger Receptor A Promotes Glial Internalization of Aβ
title_fullStr Activated Scavenger Receptor A Promotes Glial Internalization of Aβ
title_full_unstemmed Activated Scavenger Receptor A Promotes Glial Internalization of Aβ
title_sort activated scavenger receptor a promotes glial internalization of aβ
description 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.
publisher Public Library of Science
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981768/
_version_ 1612076467894616064

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