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)-κB-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.

Semi-supervised learning for potential human microRNA-disease associations inference

“…The prediction result was verified based on recent experimental literatures. As a result, in the top 3 potential related miRNA list predicted by RLSMDA for 32 diseases investigated here, 34 disease-miRNA associations were successfully confirmed by biological experiments636465666768697071727374757677787980818283848586878889909192939495 (See Table 3). …”

MicroRNA-146a Contributes to SCI Recovery via Regulating TRAF6 and IRAK1 Expression

“…Lukiw recently reported that an upregulated miRNA-146a might 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 [23]. Although accumulated evidence suggests that miRNA-146a may participate in SCI recovery [5, 8, 24], there is still limited knowledge of the miRNA-146a regulatory networks that modulate genes expression.…”

Spreading of Alzheimer’s disease inflammatory signaling through soluble micro-RNA

“…LED-Northern dot blots are a significant advancement over classical Northern blotting techniques because they utilize LNA-stabilized miRNAs or anti-miRNAs(AMs) covalently linked to a nylon-based membrane matrix (using EDC) and are probed using DIG-labeled small RNAs with fluorescent reporters [19–22]. miRNA and/or AMs, as locked nucleic acid (LNA) oligonucleotides, included a control miRNA-183 (5′-TATGGCACTGGTAGAATTCACT-3′), anti-miRNA-155 (AM-155; 5′-AATTACGATTAGCACTATCCCCA-3′), and a scrambled control AM-155 (AM-155sc; 5′-TTAACATTAGACGATATCCCACC-3′) were purchased from Applied Biosystems/Ambion, Austin, Texas, USA or Exiqon Inc., Woburn, Massachusetts, USA [11,16], and were used at a 5–20 nM ambient concentration that was replenished at every change of ABM (see above; Lonza, Basel, Switzerland) for a total treatment time of 12 and 36 h after the induction of TNF-α + Aβ42 peptide. miRNA-146a and AM-146a sequences and their usage have been described previously [12–17].…”