Mitochondrial Dysfunction and Multiple Sclerosis

Abstract

In recent years, several studies have examined the potential associations between mitochondrial dysfunction and neurodegenerative diseases such as multiple sclerosis (MS), Parkinson's disease and Alzheimer's disease. In MS, neurological disability results from inflammation, demyelination, and ultimately, axonal damage within the central nervous system. The sustained inflammatory phase of the disease leads to ion channel changes and chronic oxidative stress. Several independent investigations have demonstrated mitochondrial respiratory chain deficiency in MS, as well as abnormalities in mitochondrial transport. These processes create an energy imbalance and contribute to a parallel process of progressive neurodegeneration and irreversible disability. The potential roles of mitochondria in neurodegeneration are reviewed. An overview of mitochondrial diseases that may overlap with MS are also discussed, as well as possible therapeutic targets for the treatment of MS and other neurodegenerative conditions.

Keywords: mitochondria; multiple sclerosis; neurodegeneration; neuroinflammation.

Figure 1

Mitochondrial dysfunction described in the literature associated with Multiple Sclerosis. Chronic neuroinflammation leading to mitochondrial dysfunction.

Figure 2

The role of mitochondria in the process of neurodegeneration. a. Normal nerve. b. Site of demyelination with secondary modification of the distribution of ion channels in the nerve. c. Structural and functional modification in mitochondria caused by oxidative stress. d. Cascade of apoptosis activated by Ca²⁺. Figure reprinted with permission from the article “Involvement of Mitochondria in Neurodegeneration in Multiple Sclerosis”, Kozin et al., Biochemistry (Moscow), 2018, Vol. 83, No. 7, pp. 813–830 [4].