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Involvement of Mitochondria in Neurodegeneration in Multiple Sclerosis

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Abstract

Functional disruption and neuronal loss followed by progressive dysfunction of the nervous system underlies the pathogenesis of numerous disorders defined as “neurodegenerative diseases”. Multiple sclerosis, a chronic inflammatory demyelinating disease of the central nervous system resulting in serious neurological dysfunctions and disability, is one of the most common neurodegenerative diseases. Recent studies suggest that disturbances in mitochondrial functioning are key factors leading to neurodegeneration. In this review, we consider data on mitochondrial dysfunctions in multiple sclerosis, which were obtained both with patients and with animal models. The contemporary data indicate that the axonal degeneration in multiple sclerosis largely results from the activation of Ca2+-dependent proteases and from misbalance of ion homeostasis caused by energy deficiency. The genetic studies analyzing association of mitochondrial DNA polymorphic variants in multiple sclerosis suggest the participation of mitochondrial genome variability in the development of this disease, although questions of the involvement of individual genomic variants are far from being resolved.

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Abbreviations

AP:

action potential

BBB:

blood–brain barrier

CNS:

central nervous system

EAE:

experimental autoimmune encephalomyelitis

ETC:

electron transport chain

MBP:

myelin basic protein

MS:

multiple sclerosis

mtDNA:

mitochondrial DNA

PPMS:

primary progressive multiple sclerosis

RRMS:

relapsing-remitting multiple sclerosis

ROS:

reactive oxygen species

SNP:

single nucleotide polymorphism

SPMS:

secondary progressive multiple sclerosis

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Authors and Affiliations

  1. Pirogov Russian National Research Medical University, 117997, Moscow, Russia

    M. S. Kozin, O. G. Kulakova & O. O. Favorova

  2. National Medical Research Center of Cardiology, 121552, Moscow, Russia

    M. S. Kozin, O. G. Kulakova & O. O. Favorova

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  1. M. S. Kozin
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Original Russian Text © M. S. Kozin, O. G. Kulakova, O. O. Favorova, 2018, published in Biokhimiya, 2018, Vol. 83, No. 7, pp. 1002–1021.

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Kozin, M.S., Kulakova, O.G. & Favorova, O.O. Involvement of Mitochondria in Neurodegeneration in Multiple Sclerosis. Biochemistry Moscow 83, 813–830 (2018). https://doi.org/10.1134/S0006297918070052

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