UPREGULATION OF MICRO RNA-146a (miRNA-146a), A MARKER FOR INFLAMMATORY NEURODEGENERATION, IN SPORADIC CREUTZFELDT-JAKOB DISEASE (sCJD) AND GERSTMANN-STRAUSSLER-SCHEINKER (GSS) SYNDROME

作者：Lukiw W J^*; Dua P; Pogue A I; Eicken C; Hill J M

来源：Journal of Toxicology and Environmental Health Part A: Current Issues , 2011, 74(22-24): 1460-1468.

DOI：10.1080/15287394.2011.618973

A mouse-and human-brain-abundant, nuclear factor (NF)-kappa B-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-, A beta 42 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.

• 出版日期2011