International Journal of Molecular Sciences
The human brain and central nervous system (CNS) harbor a select sub‐group of potentially pathogenic microRNAs (miRNAs), including a well‐characterized NF‐kB‐sensitive Homo sapiens microRNA hsa‐miRNA‐146a‐5p (miRNA‐146a). miRNA‐146a is significantly over-expressed in progressive and often lethal viral‐ and prion‐mediated and related neurological syndromes associated with progressive inflammatory neurodegeneration. These include ~18 different viral‐induced encephalopathies for which data are available, at least ~10 known prion diseases (PrD) of animals and humans, Alzheimer’s disease (AD) and other sporadic and progressive age‐related neurological disorders. Despite the apparent lack of nucleic acids in prions, both DNA‐ and RNA‐containing viruses along with prions significantly induce miRNA‐146a in the infected host, but whether this represents part of the host’s adaptive immunity, innate‐immune response or a mechanism to enable the invading prion or virus a successful infection is not well understood. Current findings suggest an early and highly interactive role for miRNA‐146a: (i) as a major small noncoding RNA (sncRNA) regulator of innate‐immune responses and inflammatory signaling in cells of the human brain and CNS; (ii) as a critical component of the complement system and immune‐related neurological dysfunction; (iii) as an inducible sncRNA of the brain and CNS that lies at a critical intersection of several important neurobiological adaptive immune response processes with highly interactive associations involving complement factor H (CFH), Toll‐like receptor pathways, the innate‐immunity, cytokine production, apoptosis and neural cell decline; and (iv) as a potential biomarker for viral infection, TSE and AD and other neurological diseases in both animals and humans. In this report, we review the recent data supporting the idea that miRNA‐146a may represent a novel and unique sncRNA‐based biomarker for inflammatory neurodegeneration in multiple species. This paper further reviews the current state of knowledge regarding the nature and mechanism of miRNA‐146a in viral and prion infection of the human brain and CNS with reference to AD wherever possible.
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Pogue, Aileen I. and Lukiw, Walter J., "Microrna‐146a‐5p, Neurotropic Viral Infection and Prion Disease (Prd)" (2021). School of Medicine Faculty Publications. 197.