PMID: 22583438May 16, 2012Paper

Clonal expansion of mitochondrial DNA deletions and the progression of multiple sclerosis

CNS & Neurological Disorders Drug Targets
Graham R Campbell, D Mahad

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Mechanisms of disease progression in MS are poorly understood but are thought to relate to both focal pathology as well as diffuse inflammation in the white and grey matter. Evidence points to neurodegeneration combined with a loss of cellular function in the remaining tissue as an important factor to the progression of MS. Mitochondria are implicated to play a role in the pathogenesis of MS with evidence of loss of mitochondrial respiratory chain activity, down regulation of both nuclear DNA and mitochondrial DNA (mtDNA) encoded transcripts as well as oxidative damage to, and deletions of, the mitochondrial DNA (mtDNA). The double stranded circle of mtDNA (16.6 kb) encompasses genes encoding key subunits within the mitochondrial respiratory chain required for the production of ATP as well as transfer RNA and ribosomal RNA molecules within the cell. The stability of mtDNA is essential for a healthy CNS as highlighted by the patients with primary mitochondrial disease. In this review, we focus on the potential role of mtDNA mutations, in particular somatic mtDNA deletions, in the pathogenesis of the progressive stage of MS. We propose ...Continue Reading

Citations

Feb 24, 2016·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·A Suneetha, K Raja Rajeswari
Dec 18, 2013·Seminars in Pediatric Neurology·Karen S Carvalho
May 28, 2015·Biochimica Et Biophysica Acta·Michael J Keogh, Patrick F Chinnery
May 31, 2014·Oxidative Medicine and Cellular Longevity·Giovanni PaganoAdriana Zatterale
Dec 19, 2014·Brain Pathology·Gabriele C DeLucaSarah A Morrow
May 29, 2014·Oxidative Medicine and Cellular Longevity·Jinzhou FengXinyue Qin
Jun 22, 2013·Multiple Sclerosis : Clinical and Laboratory Research·Graham R CampbellDon J Mahad
Jan 10, 2020·Brain Pathology·Andreas JunkerChristine Stadelmann
Dec 31, 2019·F1000Research·Peter K Stys, Shigeki Tsutsui
Feb 19, 2017·The Journal of Physiology·Meneka KanagaratnamMark D Baker

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