Review: Mitochondria and disease progression in multiple sclerosis
Open Access
- 12 November 2008
- journal article
- review article
- Published by Wiley in Neuropathology and Applied Neurobiology
- Vol. 34 (6), 577-589
- https://doi.org/10.1111/j.1365-2990.2008.00987.x
Abstract
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Recent evidence suggests that dysfunction of surviving demyelinated axons and axonal degeneration contribute to the progression of MS. We review the evidence for and potential mechanisms of degeneration as well as dysfunction of chronically demyelinated axons in MS with particular reference to mitochondria, the main source of adenosine‐5′‐triphosphate in axons. Besides adenosine‐5′‐triphosphate production, mitochondria play an important role in calcium handling and produce reactive oxygen species. The mitochondrial changes in axons lacking healthy myelin sheaths as well as redistribution of sodium channels suggest that demyelinated axons would be more vulnerable to energy deficit than myelinated axons. A dysfunction of mitochondria in lesions as well as in the normal‐appearing white and grey matter is increasingly recognized in MS and could be an important determinant of axonal dysfunction and degeneration. Mitochondria are a potential therapeutic target in MS.This publication has 130 references indexed in Scilit:
- Targeting lipophilic cations to mitochondriaBiochimica et Biophysica Acta (BBA) - Bioenergetics, 2008
- Mitochondrial defects in acute multiple sclerosis lesionsBrain, 2008
- Nmnat Delays Axonal Degeneration Caused by Mitochondrial and Oxidative StressJournal of Neuroscience, 2008
- Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosisJCI Insight, 2008
- PRIMARY SPINAL CORD NEURODEGENERATION IN LEBER HEREDITARY OPTIC NEUROPATHYNeurology, 2007
- Cyclophilin D inactivation protects axons in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosisProceedings of the National Academy of Sciences of the United States of America, 2007
- Lesion genesis in a subset of patients with multiple sclerosis: a role for innate immunity?Brain, 2007
- Mitochondrial dysfunction and oxidative stress in neurodegenerative diseasesNature, 2006
- Mitochondria-targeted peptide antioxidants: Novel neuroprotective agentsThe AAPS Journal, 2006
- Mitochondrial DNA mutations in human diseaseNature Reviews Genetics, 2005