Title:Homocysteine in Neurology: From Endothelium to Neurodegeneration
Volume: 13
Issue: 3
Author(s): Rita Moretti*, Matteo Dal Ben, Silvia Gazzin and Claudio Tiribelli
Affiliation:
- Neurology Clinic, Department of Medical, Surgical, and Health Sciences, University of Trieste, Trieste,Italy
Keywords:
Homocysteine, folate, vitamin B12-cobalamin, dementias, psychiatric symptoms, vascular endothelium,
folate-vitamin B12 supplementation, therapy.
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.
