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Homocysteine in Neurology: From Endothelium to Neurodegeneration

[ Vol. 13 , Issue. 3 ]

Author(s):

Rita Moretti, Matteo Dal Ben, Silvia Gazzin and Claudio Tiribelli   Pages 163 - 175 ( 13 )

Abstract:


Vitamin B12 and folate are supplied via two major pathways, the conversion of homocysteine to methionine and the conversion of methyl malonyl coenzyme A to succinyl coenzyme A. Therefore, the defect in both the vitamins results in an increase in both serum homocysteine and methylmalonic acid. Hence, homocysteine, vitamin B12, and folate are closely linked together in the so-called one-carbon cycle, making vitamin B12 the necessary co-enzyme for the methyl donation from 5-methyl-tetra-hydrofolate in tetra-hydro-folate, necessary for methionine synthetase. Folate is a cofactor in one-carbon metabolism, and it promotes the remethylation of homocysteine, which can cause DNA strand breakage, oxidative stress and apoptosis. Vitamin B12 and folate are involved in nucleic acid synthesis and in the methylation reactions, and their deficit causes the inhibition of S-adenosylmethionine mediated methylation reactions, and through the related toxic effects of homocysteine, a possible direct alteration of the vascular endothelium and inhibition of N-methyl-D-Aspartate receptors take place. We discussed the possible and still controversial role of homocysteine accumulation in cerebral pathologies, starting from vascular events to neurodegeneration and to endothelium damage mechanism.

Keywords:

Homocysteine, folate, vitamin B12-cobalamin, dementias, psychiatric symptoms, vascular endothelium, folate-vitamin B12 supplementation, therapy.

Affiliation:

Neurology Clinic, Department of Medical, Surgical, and Health Sciences, University of Trieste, Trieste, Italian Liver Foundation, Centro Studi Fegato, SS14, Km 163.5, Trieste, 34149, Italian Liver Foundation, Centro Studi Fegato, SS14, Km 163.5, Trieste, 34149, Italian Liver Foundation, Centro Studi Fegato, SS14, Km 163.5, Trieste, 34149

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