Abstract
Endothelial dysfunction is recognized as one of the leading factors in the pathogenesis of diseases of the central nervous system of various etiologies. Numerous studies have shown the role of hyperhomocysteinemia in the development of endothelial dysfunction and the prothrombogenic state. The most important condition in the development of multiple sclerosis (MS) is a dysregulation of the blood-brain barrier (BBB) and transendothelial leukocyte migration. It has been proven that homocysteine also contributes to the damage of neurons by the mechanism of excitotoxicity and the induction of the apoptosis of neurons. These processes can be one of the factors of neurodegenerative brain damage, which plays a leading role in the progression of MS. This review describes the pleiotropic effect of homocysteine on these processes and its role in MS pathogenesis.
Highlights
Endothelial dysfunction is currently considered as one of the universal mechanisms for the development and progression of damage to the nervous system in diseases of various etiologies
One of the crucial factors in the development of endothelial dysfunction in various conditions is an increase in the content of homocysteine in the blood plasma, a sulfur-containing acid that is a product of methionine metabolism
[44] Another possible aspect of the negative effect of homocysteine in multiple sclerosis (MS) may be the hypomethylation of myelin basic protein, which develops due to a decrease in the availability of S-adenosylmethionine in hyperhomocysteinemia, which leads to the destabilization of the myelin structure [45,46]
Summary
Endothelial dysfunction is currently considered as one of the universal mechanisms for the development and progression of damage to the nervous system in diseases of various etiologies. A large number of experimental and clinical studies have convincingly shown that the development of endothelial dysfunction is an important factor in the pathogenesis of vascular and autoimmune and neurodegenerative diseases [1,2]. This review describes the pleiotropic effect of homocysteine on these processes and its role in multiple sclerosis (MS) pathogenesis
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