Multiple Sclerosis and mitochondrial gene variation: A systematic review

Background and Objectives: As an autoimmune neurodegenerative inflammatory disease of the CentralNervous System (CNS), Multiple Sclerosis (MS), has been considered at topics of global health system concerns.In spite of currently approved therapeutic strategies for MS, there is no definite cure, in which, mostly adults areinvolved with severe and progressive forms of the disease. Meanwhile, the modest heritability of MS highlightsus complex genetics, multifaceted nuclear and mitochondrial interactions. So, this study overviews thegenomic variations to decipher MS pathogenesis.Search method: This systematic review was conducted to outline comprehensive studies published in PubMed,Scopus, Science Direct, Medline databases and Google Scholar search engine from 2008 up to May 2017 byusing 4 keywords (MeSH Terms). Then, 123 articles were screened and 54 were totally included.Results: Dealing with mentioned challenges on MS, clinical researches focused on correlation betweenvulnerability to MS and some mitochondrial dysfunctions as a pivotal organelle in neuro-pathologic conditions.Molecular studies demonstrated that abnormalities in mitochondrial dynamics, impact cellular pathways such asinflammation and demyelination in MS patients. mtDNA defects, abnormal mitochondrial gene expression,defective mitochondrial enzyme activities, deficient mtDNA repair activity, and mitochondrial dysfunctions havebeen shown to play a role in MS progression. For example, abnormalities in complex I subunits can lead toneurodegeneration and demyelization. Biochemical studies have shown that catalytic activity of complex I issignificantly decreased in MS patients. Furthermore, haplotype analysis and restriction site polymorphisms haverevealed that mtDNA haplogroups K and J are associated with MS. Patients with haplogroup J variants were at a1.5-times increased risk for developing primary progressive MS.Conclusion: Frustrating dilemma on complicated etiopathogenesis of MS, represent identification andmodifications on variations in mtDNA and nuclear encoded mitochondrial genes. This, may lead to new optimistictargeted therapy through a robust collaboration between specialist, molecular geneticist and immunobiologists inorder to diagnose accurately and diminish imposed costs of MS patients.

Keywords:

Multiple Sclerosis , Pathogenesis , Mitochondrial gene variation , Mitochondrial DNA