title: Blockage of CR1 prevents activation of rodent microglia.
abstract: The importance of the complement system in Alzheimer's disease (AD) pathogenesis has been emphasized through recent genome wide association studies. However, the cellular and molecular role of these complement proteins is not fully understood. Microglia express complement receptors and the activation of specific receptors may increase Aβ clearance and reduce neurodegeneration. Here, we investigated the contribution of complement receptor 1 (CR1), the second most significant hit in GWAS studies, on microglia to neuronal damage. We show that microglia displaying an activated phenotype demonstrate an increase in CR1 expression. We also provide evidence that activation of microglial CR1 was detrimental to neurons and this correlated with an increase in microglial intracellular superoxide generation, and tumour necrosis factor-α (TNFα) and interleukin-1 β (IL-1β) secretion. Amyloid-β 42 (Aβ1-42)-treated microglia displayed an increased ability to phagocytose dextran beads following antibody blockage of CR1 but a decreased capacity to phagocytose fluorescent-tagged Aβ1-42. Together, these results indicate that microglial CR1 plays a role in the neuronal death observed in AD and investigating this further may provide a possible strategy to control neurotoxicity in the AD brain.
authors: Department of Neuroinflammation, University College London, Institute of Neurology, 1 Wakefield Street, London WC1 N1PJ, UK.
authors: Helen
authors: H
authors: Crehan
authors: John
authors: J
authors: Hardy
authors: Jennifer
authors: J
authors: Pocock
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D017628:Microglia / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism*; D014162:Transfection
chemical_list: D016207:Cytokines; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D011951:Receptors, Complement