title: Gold drug auranofin could reduce neuroinflammation by inhibiting microglia cytotoxic secretions and primed respiratory burst.
abstract: Neuroinflammation contributes to the pathogenesis of neurological disorders. Anti-inflammatory treatments could potentially be used to slow down the progression of these diseases. We studied the anti-neuroinflammatory activity of gold compounds which have been used to treat rheumatoid arthritis. Non-toxic concentrations of auranofin (0.1-1 μM) significantly reduced the cytotoxic secretions by primary human microglia and microglia-like THP-1 promonocytic cells. Auranofin inhibited primed NADPH-oxidase dependent respiratory burst and secretion of tumor necrosis factor (TNF)-α and nitric oxide by monocytic cells. It had a direct neuroprotective effect on SH-SY5Y neuronal cells. Auranofin could have a novel application in the treatment of neurodegenerative diseases.
authors.affiliation: Department of Biology, University of British Columbia Okanagan Campus, Kelowna, BC, Canada.
authors.forename: Jocelyn M
authors.initials: JM
authors.lastname: Madeira
authors.affiliation: Department of Biology, University of British Columbia Okanagan Campus, Kelowna, BC, Canada.
authors.forename: Ekta
authors.initials: E
authors.lastname: Bajwa
authors.affiliation: Department of Biology, University of British Columbia Okanagan Campus, Kelowna, BC, Canada.
authors.forename: Maegan J
authors.initials: MJ
authors.lastname: Stuart
authors.affiliation: Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada; Department of Psychiatry, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan.
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Hashioka
authors.affiliation: Department of Biology, University of British Columbia Okanagan Campus, Kelowna, BC, Canada. Electronic address: andis.klegeris@ubc.ca.
authors.forename: Andis
authors.initials: A
authors.lastname: Klegeris
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001310:Auranofin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D042381:Granulocyte Precursor Cells / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects; D019255:NADPH Oxidases / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D013702:Temporal Lobe / Q000166:cytology; D013997:Time Factors
chemical_list: D018501:Antirheumatic Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D001310:Auranofin; D007770:L-Lactate Dehydrogenase; D019255:NADPH Oxidases
keywords: Alzheimer's disease; Aurothiomalate; Aurothiosulfate; Neuroprotection; Parkinson's disease; Respiratory burst priming