title: Amyloid-β Activates Microglia and Regulates Protein Expression in a Manner Similar to Prions.
abstract: Prions are the only convincingly demonstrated proteinaceous infectious particle, yet recent studies find that amyloid-β peptide (Aβ) aggregates are capable of self-propagation, which induces amyloidosis pathology in Alzheimer's disease (AD) model mice that is similar to the self-propagation phenomenon of prions in neurons. Gliosis is a common hallmark of AD and prion diseases, in which activated microglia accumulate around abnormal protein deposits. Analyses of the characteristics of activated microglia induced by Aβ in comparison with those induced by prions will provide new insight into the pathogenesis of AD. Therefore, we compared the characteristics of BV-2 cells (model microglia) activated by Aβ fibrillar peptides (Aβ1-42) and prions (PrP106-126). Aβ1-42 and PrP106-126, as well as the supernatants of the media collected from BV-2 cells cocultured with Aβ1-42 and PrP106-126, were potent activators of BV-2 microglial activity, but the chemotaxis index (CI) induced by Aβ1-42 was significantly higher than that induced by PrP106-126 at each concentration. Aβ1-42 and PrP106-126 increased the proliferation index (PI) and upregulated monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor beta 1 (TGF-β1) expression after 12 h of exposure. Our results show that Aβ activates microglia and regulates microglial protein expression in a manner similar to prions and, thus, provide new insight into the pathogenesis of AD.
authors: State Key Laboratories for Agrobiotechnology, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, 100193, Beijing, China, tujian1980@126.com.
authors: Jian
authors: J
authors: Tu
authors: Baian
authors: B
authors: Chen
authors: Lifeng
authors: L
authors: Yang
authors: Kezong
authors: K
authors: Qi
authors: Jing
authors: J
authors: Lu
authors: Deming
authors: D
authors: Zhao
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000633:toxicity*; D011328:Prions / Q000633:toxicity*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016229:Amyloid beta-Peptides; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D010446:Peptide Fragments; D011328:Prions; D053773:Transforming Growth Factor beta1; C075222:amyloid beta-protein (1-42); C082632:prion protein (106-126)