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.

Keywords: autoimmunity; biomarkers; miR-155; microRNA (miRNA); multiple sclerosis (MS); neuroinflammation.

Figure 1

Operation of miR-155 in disruption of the BBB under inflammatory conditions. miR-155 is up-regulated due to pro-inflammatory cytokines activity, such as TNF-α and IFN-γ. Overexpression of miR-155 enhances an inflammatory effect contributing indirectly to BBB permeability via down-regulation of junctional proteins between endothelial cells: CLDN-1, ANXA-2, SDCBP, and DOCK-1. Abbreviations: BBB—blood–brain barrier; TNF-α—tumor necrosis factor-α; IFN-γ—interferon-γ; CLDN-1—claudin-1; ANXA-2—annexin-2; SDCBP—syntenin-1, DOCK-1—dedicator of cytokinesis-1.