Activated scavenger receptor A promotes glial internalization of aβ

• Published in: PloS one 2014-04, Vol.9 (4), p.e94197
• Main Authors: Zhang, He, Su, Ya-jing, Zhou, Wei-wei, Wang, Shao-wei, Xu, Peng-xin, Yu, Xiao-lin, Liu, Rui-tian
• Format: Article
• Language: English
• Subjects: Aggregates; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animals; Astrocytes; Astrocytes - drug effects; Astrocytes - metabolism; Astrocytoma - pathology; Biocompatibility; Brain; Care and treatment; Cascades; Cell Line; Cell Line, Tumor; Cells, Cultured; Cerebral Cortex - cytology; Chemokines; Cytokines; Cytotoxicity; Diagnosis; Drug Evaluation, Preclinical; Gene expression; Glial cells; Humans; IL-1β; Inflammation; Interleukin-1beta - secretion; Internalization; Intracellular signalling; Kinases; Laboratories; Ligands; Macrophages; MAP kinase; Medicine and Health Sciences; Membrane Proteins - metabolism; Mice; Microglia; Microglia - drug effects; Microglia - metabolism; Monomers; Neurodegenerative diseases; Neuroprotection; Pathogenesis; Peptide Fragments - metabolism; Peptides; Peptides - pharmacology; Phagocytosis; Phagocytosis - drug effects; Prevention; Process engineering; Protein kinase; Proteins; Rats; Receptors, Scavenger - physiology; Risk factors; Rodents; Scavenger receptors; Scavenger Receptors, Class A - physiology; Toxicity; Transgenic animals; Tumor Necrosis Factor-alpha - secretion; Tumor necrosis factor-α; β-Amyloid
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0094197

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.