miR-155 as an Important Regulator of Multiple Sclerosis Pathogenesis. A Review

Abstract

Multiple sclerosis (MS) is a chronic, immune-mediated disease and the leading cause of disability among young adults. MicroRNAs (miRNAs) are involved in the post-transcriptional regulation of gene expression. Of them, miR-155 is a crucial regulator of inflammation and plays a role in modulating the autoimmune response in MS. miR-155 is involved in blood–brain barrier (BBB) disruption via down-regulation of key junctional proteins under inflammatory conditions. It drives demyelination processes by contributing to, e.g., microglial activation, polarization of astrocytes, and down-regulation of CD47 protein and affecting crucial transcription factors. miR-155 has a huge impact on the development of neuropathic pain and indirectly influences a regulatory T (Treg) cell differentiation involved in the alleviation of pain hypersensitivity. This review also focused on neuropsychiatric symptoms appearing as a result of disease-associated stressors, brain atrophy, and pro-inflammatory factors. Recent studies revealed the role of miR-155 in regulating anxiety, stress, inflammation in the hippocampus, and treatment-resistant depression. Inhibition of miR-155 expression was demonstrated to be effective in preventing processes involved in the pathophysiology of MS. This review aimed to support the better understanding the great role of miR-155 dysregulation in various aspects of MS pathophysiology and highlight future perspectives for this molecule.

Non-coding RNAs in the regulation of blood–brain barrier functions in central nervous system disorders

“…miR-155 exhibited upregulated cerebral expression in MS patients or experimental models [ 171 – 173 ]. Lopez-Ramirez et al showed that loss of miR-155 reduced BBB extravasation of both experimental autoimmune encephalomyelitis (EAE) and in an acute systemic inflammation model induced by lipopolysaccharide [ 172 ].…”

The functional mechanisms of synchronizing royal jelly consumption and physical activity on rat with multiple sclerosis-like behaviors hallmarks based on bioinformatics analysis, and experimental survey

“…On the other hand, the literature review highlighted that miR-155 is a pivotal regulator in the inflammation pathway and modulated an autoimmune response. Furthermore, a recent study had shown that inhibition of miR-155 led to the prevention of pathophysiological mechanisms involved in multiple sclerosis incidence [ 48 ]. Moreover, Forough Taheri reported that miR-34 has a potential role in Th17 cell differentiation induction, and up-regulation of miR-34 could lead to progressive multiple sclerosis status, and down-regulation of miR-34 might ameliorate multiple sclerosis condition [ 49 ].…”

Extracellular Vesicles in Multiple Sclerosis: Role in the Pathogenesis and Potential Usefulness as Biomarkers and Therapeutic Tools

“…Comparing EV miRNA profiles among the spinal cord (SP), plasma, and urine at the pre-onset, onset, and peak stages of EAE disease, the authors found an overexpression of EV-derived miR-155-5p during pre-onset [ 66 ]. This miRNA, also known as inflamma-miR, is a strong regulator of inflammation, modulating the autoimmune response in MS [ 80 ]. They also examined the effect of glatimer acetate (GA), usually used in MS therapy, on miRNA expression, showing, for the first time, that under treatment, especially in urinary EV miRNAs, expression was modulated, and miR-9-5p and miR-35-3p were significantly deregulated at the EAE peak stage.…”