Abstract
Multiple sclerosis (MS) is a debilitating neurodegenerative, highly heterogeneous disease with a variable course. The most common MS subtype is relapsing–remitting (RR), having interchanging periods of worsening and relative stabilization. After a decade, in most RR patients, it alters into the secondary progressive (SP) phase, the most debilitating one with no clear remissions, leading to progressive disability deterioration. Among the greatest challenges for clinicians is understanding disease progression molecular mechanisms, since RR is mainly characterized by inflammatory processes, while in SP, the neurodegeneration prevails. This is especially important because distinguishing RR from the SP subtype early will enable faster implementation of appropriate treatment. Currently, the MS course is not well-correlated with the biomarkers routinely used in clinical practice. Despite many studies, there are still no reliable indicators correlating with the disease stage and its activity degree. Circulating microRNAs (miRNAs) may be considered valuable molecules for the MS diagnosis and, presumably, helpful in predicting disease subtype. MiRNA expression dysregulation is commonly observed in the MS course. Moreover, knowledge of diverse miRNA panel expression between RRMS and SPMS may allow for deterring disability progression through successful treatment. Therefore, in this review, we address the current state of research on differences in miRNA panel expression between the phases.
Highlights
Multiple sclerosis (MS) is an autoimmune disease characterized by chronic inflammation, demyelination, and neurodegeneration of the central nervous system (CNS) [1]
The findings suggest significant differences in the expression of many miRNAs between relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) subtypes
There is no sufficient data that would support the association of the expression level of specific circulating miRNA molecules with the development of pathological processes characteristic of particular stages of the MS course
Summary
Multiple sclerosis (MS) is an autoimmune disease characterized by chronic inflammation, demyelination, and neurodegeneration of the central nervous system (CNS) [1]. The remaining 10–15% of MS patients develop primary progressive multiple sclerosis (PPMS), characterized by slowly worsening symptoms from the beginning, without prior or intermittent exacerbations and remissions [9] This is the result of its very heterogeneous, multifactorial etiopathogenesis and unpredictable disease course, in which several clinical phenotypes with distinct underlying pathogenic mechanisms can be distinguished [9,10,11,12]. Pasquali et al reported that the plasmatic levels of proinflammatory cytokines, both IFN-γ and IL-17, are higher in RRMS compared to SPMS patients, while the level of transforming growth factor-β (TGF-β), a molecule with immunosuppressant activity, was much lower in RRMS in comparison to SPMS [35] Another group of active molecules indicated in the literature are light neurofilaments (NFL) and glial fibrillary acid protein (GFAP), a marker of astrocyte damage and astrogliosis, in serum [36,37]. Recent studies have demonstrated that altered expression of some miRNAs may serve as valuable biomarkers to diagnose MS, and rapidly and effectively distinguish RR from the SP phase [40,41]
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