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Multiple sclerosis (MS) is the most common autoimmune inflammatory demyelinating disease that affects the brain and spinal cord.
Dysregulation or mutation of miRNA genes have been linked to the pathogenesis of MS. The miRNAs are short, 20-22 nucleotide long, single-stranded regulatory and non-protein coding RNAs that modulate the expression of multiple target genes. Among miRNAs, miR-223 has been reported to play a critical role in MS.
This review concentrates on the emerging role of miR-223 in inflammatory responses and specifically discusses how alterations in miR-223 expression are associated with the development of MS. This review also suggests that miR-223 can be used as a biomarker for diagnosis of MS and discovering novel therapeutics for MS treatment.
According to current literature, it is now increasingly evidenced that miR-223 is involved in the pathogenesis of MS. As stated above, miR-223 is highly dysregulated in MS patients as well as EAE mouse models. It might have the potential to generate a further understanding of the mechanisms underlying MS. The miR-223 has been reported to be upregulated in T-reg cells, plasma, blood cells, PBMCs and brain white matter tissue from MS patients and EAE mice. Such reports provide evidence that miR-223 may be a suitable choice for further studies as a novel therapeutic goal. It can also be used as a biomarker for diagnosis and monitor disease status in MS and a prognostic marker of treatment responsiveness.
Division of BioMedical Sciences, Faculty of Medicine, Newfoundland, Canada
miR-223 promotes regenerative myeloid cell phenotype and function in the demyelinated central nervous system
In the injured central nervous system, myeloid cells, including macrophages and microglia, are key contributors to both myelin injury and repair. This immense plasticity emphasizes the need to further understand the precise molecular mechanisms that contribute to the dynamic regulation of myeloid cell polarization and function. Herein, we demonstrate that miR-223 is upregulated in multiple sclerosis (MS) patient monocytes and the alternatively-activated and tissue-regenerating M2-polarized human macrophages and microglia. Using miR-223 knock-out mice, we observed that miR-223 is dispensable for maximal pro-inflammatory responses, but is required for efficient M2-associated phenotype and function, including phagocytosis. Using the lysolecithin animal model, we further demonstrate that miR-223 is required to efficiently clear myelin debris and promote remyelination. These results suggest miR-223 constrains neuroinflammation while also promoting repair, a finding of important pathophysiological relevance to MS as well as other neurodegenerative diseases.
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