title: Upregulation of micro RNA-146a (miRNA-146a), a marker for inflammatory neurodegeneration, in sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Straussler-Scheinker (GSS) syndrome.
abstract: A mouse- and human-brain-abundant, nuclear factor (NF)-кB-regulated, micro RNA-146a (miRNA-146a) is an important modulator of the innate immune response and inflammatory signaling in specific immunological and brain cell types. Levels of miRNA-146a are induced in human brain cells challenged with at least five different species of single- or double-stranded DNA or RNA neurotrophic viruses, suggesting a broad role for miRNA-146a in the brain's innate immune response and antiviral immunity. Upregulated miRNA-146a is also observed in pro-inflammatory cytokine-, Aβ42 peptide- and neurotoxic metal-induced, oxidatively stressed human neuronal-glial primary cell cocultures, in murine scrapie and in Alzheimer's disease (AD) brain. In AD, miRNA-146a levels are found to progressively increase with disease severity and co-localize to brain regions enriched in inflammatory neuropathology. This study provides evidence of upregulation of miRNA-146a in extremely rare (incidence 1-10 per 100 million) human prion-based neurodegenerative disorders, including sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Straussler-Scheinker syndrome (GSS). The findings suggest that an upregulated miRNA-146a may be integral to innate immune or inflammatory brain cell responses in prion-mediated infections and to progressive and irreversible neurodegeneration of both the murine and human brain.
authors: LSU Neuroscience Center and Departments of Ophthalmology, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, LA70112-2272, USA. wlukiw@lsuhsc.edu
authors: W J
authors: WJ
authors: Lukiw
authors: P
authors: P
authors: Dua
authors: A I
authors: AI
authors: Pogue
authors: C
authors: C
authors: Eicken
authors: J M
authors: JM
authors: Hill
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D007562:Creutzfeldt-Jakob Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016098:Gerstmann-Straussler-Scheinker Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020078:Neurogenic Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)