title: Silencing of the P2X(7) receptor enhances amyloid-β phagocytosis by microglia.
abstract: P2X7 receptor (P2X7R) is an ATP-gated cation channel that promotes microglia activation and plays a critical role in the pathogenesis of Alzheimer's disease. Inhibiting P2X7R indirectly reduces the rate of amyloid-β (Aβ)-induced neurodegeneration by suppressing secretion of inflammatory factors from activated microglia. We used RNA interference to silence P2X7R in microglial cells in vitro and found it markedly increased microglial phagocytosis of Aβ1-42. Increased phagocytic activity was dependent on decreasing the rate of interleukin-1β release from microglia and required inhibition of the COX-2 pathway. Modulation of microglial phagocytosis and secretion via silencing P2X7R may be a promising therapeutic option for the treatment of Alzheimer's disease.
authors.affiliation: Department of Medical Imaging, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Ni
authors.forename: Peijun
authors.initials: P
authors.lastname: Wang
authors.forename: Jingfa
authors.initials: J
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Limin
authors.initials: L
authors.lastname: Gu
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2 / Q000378:metabolism; D020868:Gene Silencing; D007150:Immunohistochemistry; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D010587:Phagocytosis; D061251:Primary Cell Culture; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism*; D012394:Rosaniline Dyes / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: C501048:3-(4-methylsulfonylphenyl)-4-phenyl-5-trifluoromethylisoxazole; D016229:Amyloid beta-Peptides; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D007555:Isoxazoles; D008565:Membrane Proteins; D010446:Peptide Fragments; D058920:Purinergic P2X Receptor Antagonists; D034741:RNA, Small Interfering; D058486:Receptors, Purinergic P2X7; D012394:Rosaniline Dyes; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse; C004692:coomassie Brilliant Blue