Elucidating the Molecular Basis of Multiple Sclerosis and Understanding the Disease Pathophysiology

Abstract

Multiple sclerosis (MS) is a complex, multifactorial autoimmune disorder of the central nervous system (CNS) that causes inflammation, demyelination and neurodegeneration. The increased prevalence of this disease in Arabian Gulf Countries (AGCs) has captivated the author. The following is a deliberative review of the disease with respect to its molecular basis. Briefly, it considers disease pathophysiology though the molecular composition of the cell; the genome, epigenome and mitochondrial genome; and relates these factors to environmental, etiological factors, including: vitamin D, UVR, EBV infection, smoking and obesity. All in all, this review aims to explain the reasons underlying the increasing prevalence of MS in AGCs.

3DFAACTS-SNP: Using Regulatory T Cell-specific Epigenomics Data to Uncover Candidate Mechanisms of Type-1 Diabetes (T1D) risk

“…We identified putative target genes for these disease associated variants by Hi-C interactions resulting in 24, 8 and 8 genes linked to MS, 4AI and 5ID respectively (Additional file 7: Table S8). Many of these genes have either known roles in Treg differentiation, stability and function (GATA3 and CD84, ITCH, ILIRL2 and ILST) [77][78][79][80][81][82][83][84][85], or altered expression in human Treg in autoimmune-disease (ICA1, SESN3 and DLEU1) [86][87][88] and animal models of autoimmunity (SEPTIN7 and WWOX) [89].…”

Environmental Influencers, MicroRNA, and Multiple Sclerosis

“…24,26,220,224 Also, miR-155 was significantly increased in RRMS cases (Table 2). 2,130,145 Moreover, evidence associating the EBV viral protein, LMP1, to the suppression of host miR-1 is reported. LMP1 can increase the expression of phos-Stat-3 (the active form of Stat-3).…”

“…Upregulation of this miR-34a can release MØ from their inhibitory status and increase their phagocytic activity against myelin sheaths. 2,25,136 miR-34a is also predicted to target several MS risk genes, including SLC2A4RG, MYB, FOXP1, TNFSF14, and OLIG3. These genes were identified as MS risk factors through the work of IMSGC, and some of them were further confirmed through GWS analysis.…”

“…A comprehensive list of search terms was developed by the author. Keyword searches included (1) multiple sclerosis or its variants (eg multiple sclerosis, MS; relapsing-remitting multiple sclerosis, RRMS; secondary progressive multiple sclerosis, SPMS; primary progressive multiple sclerosis, PPMS; experimental autoimmune encephalomyelitis, EAE) combined with microRNA or its variant terms (eg, multiple sclerosis miRNA, multiple sclerosis microRNA), (2) any term that reflected one of the three environmental factors included in this review (eg, vitamin D; EBV; cigarette smoking) combined with micro-RNA or its variant terms (eg, vitamin D microRNA), (3) any term that defines multiple sclerosis or its variants combined with one of the three environmental factors and microRNA or its variant terms, (eg, vitamin D microRNA multiple sclerosis), (4) any term that reflected multiple sclerosis or its variants combined with the word therapy or its variant terms (eg, therapy, drug, medicine) and microRNA or its variant terms (eg, multiple sclerosis drug microRNA), and (5) any term that reflected one of the three environmental factors combined with the word therapy or its variants and microRNA or its variant terms (eg, EBV drug microRNA).…”

“…Environmental factors, such as vitamin D deficiency, Epstein-Barr virus (EBV) infection, and cigarette smoking have been confirmed to be associated with MS; however, the mechanisms by which such variants influence disease pathophysiology are still unclear. 1-21 Several theories have been previously proposed; herein, the author proposes a new theory linked to microRNA (miRNA) biogenesis. In this review, the author explores the influence of environmental variants on the miRNA network that could affect MS pathogenesis.…”