eISSN: 1509-572x
ISSN: 1641-4640
Folia Neuropathologica
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vol. 60
Original paper

microRNA-146a as a biomarker for transmissible spongiform encephalopathy

Aileen I. Pogue
Yuhai Zhao
Walter J. Lukiw

Alchem Biotech, Toronto, Canada
LSU Neuroscience Center, and Departments of Cell Biology and Anatomy, LSU Health Science Center, New Orleans, USA
LSU Neuroscience Center, and Departments of Neurology and Ophthalmology, LSU Health Sciences Center, New Orleans, USA
Folia Neuropathol 2022; 60 (1): 24-34
Online publish date: 2022/03/03
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The pro-inflammatory, innate-immune system ribonucleic acid mediator microRNA-146a, constitutively expressed in the brain and central nervous system (CNS) of both the mouse and the human, is pathologically up-regulated in multiple transmissible spongiform encephalopathies (TSEs) to several times its basal level. miRNA-146a: (i) exists as a ~22-ribonucleotide (nt) single-stranded non-coding RNA (sncRNA) whose sequence is unique and highly selected over evolution; (ii) is brain-, CNS- and lymphoid-tissue enriched and exhibits a 100% RNA sequence homology between the mouse and the human; (iii) has been repeatedly shown to play critical immunological and pro-inflammatory roles in the onset and propagation of several human CNS disorders including progressive, incapacitating, and lethal neurological syndromes that include prion disease (PrD) and Alzheimer’s disease (AD); (iv) is a fascinating molecular entity because it is representative of the smallest class of soluble, information-carrying, amphipathic sncRNA yet described; (v) has capability to be induced by cellular stressors and the pro-inflammatory transcription factor NF-kB (p50/p65); (vi) has capability to post-transcriptionally regulate multiple mRNAs and cellular processes in neurological health and disease; (vii) is upregulated in human host cells after viral invasion by single-stranded RNA (ssRNA) or double-stranded DNA (dsDNA) neurotropic viruses; and (viii) has an immense potential in neuro-degenerative disease therapeutics via anti-NF-kB and/or anti-miRNA-146a treatment strategies. In this short communication we provide for the first time evidence that miRNA-146a is a prominent sncRNA species in experimental murine prion disease, progressively increasing in the pre-symptomatic stages in C57BL/6J, SJL/J or Swiss Albino murine scrapie prion models. The highest miRNA-146a levels were quantified in these three different murine scrapie models exhibiting full symptomology of prion infection. The results suggest that miRNA-146a levels in the brain may be useful as an accessory diagnostic, prognostic or response-to-treatment biomarker to monitor the onset and development of PrD in experimental murine models that may also be extrapolated to be a relevant adjunct biomarker in human TSEs.

aging, microRNA-146a, prion disease, Alzheimer’s-disease, bovine spongiform encephalopathy, Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, NF-kB-(p50/p65), scrapie

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