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Homocysteine in Neurology: A Possible Contributing Factor to Small Vessel Disease

Homocysteine (Hcy) is a sulfur-containing amino acid generated during methionine metabolism, accumulation of which may be caused by genetic defects or the deficit of vitamin B12 and folate. A serum level greater than 15 micro-mols/L is defined as hyperhomocysteinemia (HHcy). Hcy has many roles, the...

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Autores principales: Moretti, Rita, Giuffré, Mauro, Caruso, Paola, Gazzin, Silvia, Tiribelli, Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922986/
https://www.ncbi.nlm.nih.gov/pubmed/33669577
http://dx.doi.org/10.3390/ijms22042051
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author Moretti, Rita
Giuffré, Mauro
Caruso, Paola
Gazzin, Silvia
Tiribelli, Claudio
author_facet Moretti, Rita
Giuffré, Mauro
Caruso, Paola
Gazzin, Silvia
Tiribelli, Claudio
author_sort Moretti, Rita
collection PubMed
description Homocysteine (Hcy) is a sulfur-containing amino acid generated during methionine metabolism, accumulation of which may be caused by genetic defects or the deficit of vitamin B12 and folate. A serum level greater than 15 micro-mols/L is defined as hyperhomocysteinemia (HHcy). Hcy has many roles, the most important being the active participation in the transmethylation reactions, fundamental for the brain. Many studies focused on the role of homocysteine accumulation in vascular or degenerative neurological diseases, but the results are still undefined. More is known in cardiovascular disease. HHcy is a determinant for the development and progression of inflammation, atherosclerotic plaque formation, endothelium, arteriolar damage, smooth muscle cell proliferation, and altered-oxidative stress response. Conversely, few studies focused on the relationship between HHcy and small vessel disease (SVD), despite the evidence that mice with HHcy showed a significant end-feet disruption of astrocytes with a diffuse SVD. A severe reduction of vascular aquaporin-4-water channels, lower levels of high-functioning potassium channels, and higher metalloproteinases are also observed. HHcy modulates the N-homocysteinylation process, promoting a pro-coagulative state and damage of the cellular protein integrity. This altered process could be directly involved in the altered endothelium activation, typical of SVD and protein quality, inhibiting the ubiquitin-proteasome system control. HHcy also promotes a constant enhancement of microglia activation, inducing the sustained pro-inflammatory status observed in SVD. This review article addresses the possible role of HHcy in small-vessel disease and understands its pathogenic impact.
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spelling pubmed-79229862021-03-03 Homocysteine in Neurology: A Possible Contributing Factor to Small Vessel Disease Moretti, Rita Giuffré, Mauro Caruso, Paola Gazzin, Silvia Tiribelli, Claudio Int J Mol Sci Review Homocysteine (Hcy) is a sulfur-containing amino acid generated during methionine metabolism, accumulation of which may be caused by genetic defects or the deficit of vitamin B12 and folate. A serum level greater than 15 micro-mols/L is defined as hyperhomocysteinemia (HHcy). Hcy has many roles, the most important being the active participation in the transmethylation reactions, fundamental for the brain. Many studies focused on the role of homocysteine accumulation in vascular or degenerative neurological diseases, but the results are still undefined. More is known in cardiovascular disease. HHcy is a determinant for the development and progression of inflammation, atherosclerotic plaque formation, endothelium, arteriolar damage, smooth muscle cell proliferation, and altered-oxidative stress response. Conversely, few studies focused on the relationship between HHcy and small vessel disease (SVD), despite the evidence that mice with HHcy showed a significant end-feet disruption of astrocytes with a diffuse SVD. A severe reduction of vascular aquaporin-4-water channels, lower levels of high-functioning potassium channels, and higher metalloproteinases are also observed. HHcy modulates the N-homocysteinylation process, promoting a pro-coagulative state and damage of the cellular protein integrity. This altered process could be directly involved in the altered endothelium activation, typical of SVD and protein quality, inhibiting the ubiquitin-proteasome system control. HHcy also promotes a constant enhancement of microglia activation, inducing the sustained pro-inflammatory status observed in SVD. This review article addresses the possible role of HHcy in small-vessel disease and understands its pathogenic impact. MDPI 2021-02-19 /pmc/articles/PMC7922986/ /pubmed/33669577 http://dx.doi.org/10.3390/ijms22042051 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Moretti, Rita
Giuffré, Mauro
Caruso, Paola
Gazzin, Silvia
Tiribelli, Claudio
Homocysteine in Neurology: A Possible Contributing Factor to Small Vessel Disease
title Homocysteine in Neurology: A Possible Contributing Factor to Small Vessel Disease
title_full Homocysteine in Neurology: A Possible Contributing Factor to Small Vessel Disease
title_fullStr Homocysteine in Neurology: A Possible Contributing Factor to Small Vessel Disease
title_full_unstemmed Homocysteine in Neurology: A Possible Contributing Factor to Small Vessel Disease
title_short Homocysteine in Neurology: A Possible Contributing Factor to Small Vessel Disease
title_sort homocysteine in neurology: a possible contributing factor to small vessel disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922986/
https://www.ncbi.nlm.nih.gov/pubmed/33669577
http://dx.doi.org/10.3390/ijms22042051
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