Mechanisms of Toxic Effects of Homocysteine on the Nervous System

Abstract

The role of homocysteine in neurochemical and neurophysiological processes in mammalians, including humans, is difficult to overestimate. The metabolism of homocysteine is mostly based on its re-methylation and trans-sulfonation occurring at sufficient levels of vitamins B6, B12, and that of folic acid (vitamin B9). The balance between the above-mentioned processes crucially determines the level of homocysteine in the organism. The effects of this compound on nerve tissues in the case of its excessive amount may be due to direct neurotoxic effects or are mediated by vascular mechanisms. Homocysteine affects many physiological processes in the human organism. A high level of homocysteine causes a direct cytotoxic effect on the endothelium, which simultaneously increases the consumption of nitric oxide and initiates the release of cytokines, cyclins, and other mediators of inflammation. Also, it causes excessive proliferation of smooth muscle cells of the vascular wall and of endotheliocytes, acts as a procoagulant, increases the concentrations of low-density and very-low-density lipoproteins, and reduces the production of endothelium-derived relaxing factor and sulfated glycosaminoglycans. Thus, the role of hyperhomocysteinemia in pathological events in the vascular system is twofold. First, it damages the endothelium, which is associated with early atherogenesis, and second, it increases the probability of development of thrombosis in veins and arteries, including cerebral ones.