Abstract
Hyperhomocysteinemia is a risk factor for a number of neurodegenerative and cardiovascular diseases. We have shown that homocysteine induces excitotoxic effects in cells expressing glutamate receptors of the NMDA class. These receptors were found not only in neurons but also in immune-competent cells, neutrophils, red blood cells, cardiomyocytes, and osteoblasts. Activation of these cells by homocysteine results in an increase in cytoplasmic calcium ions, accumulation of reactive oxygen species, and activation of MAP kinase. An overload of immune-competent cells activates both necrotic and apoptotic cell death, whereas the neuropeptide carnosine (an antioxidant and immune modulator) protects cells against both processes. In a model of prenatal hyperhomocysteinemia in rats, we have found that carnosine protects animals against homocysteine toxicity with no change of the blood homocysteine levels. The efficiency of carnosine has also been demonstrated in clinical trials of chronic brain ischemia and Parkinson’s disease.
Keywords: Homocysteine, homocysteic acid, NMDA receptors, neurons, immune competent cells, carnosine.
Current Aging Science
Title:Why Is Homocysteine Toxic for the Nervous and Immune Systems?
Volume: 6 Issue: 1
Author(s): Alexander Boldyrev, Ekaterina Bryushkova, Anna Mashkina and Elizaveta Vladychenskaya
Affiliation:
Keywords: Homocysteine, homocysteic acid, NMDA receptors, neurons, immune competent cells, carnosine.
Abstract: Hyperhomocysteinemia is a risk factor for a number of neurodegenerative and cardiovascular diseases. We have shown that homocysteine induces excitotoxic effects in cells expressing glutamate receptors of the NMDA class. These receptors were found not only in neurons but also in immune-competent cells, neutrophils, red blood cells, cardiomyocytes, and osteoblasts. Activation of these cells by homocysteine results in an increase in cytoplasmic calcium ions, accumulation of reactive oxygen species, and activation of MAP kinase. An overload of immune-competent cells activates both necrotic and apoptotic cell death, whereas the neuropeptide carnosine (an antioxidant and immune modulator) protects cells against both processes. In a model of prenatal hyperhomocysteinemia in rats, we have found that carnosine protects animals against homocysteine toxicity with no change of the blood homocysteine levels. The efficiency of carnosine has also been demonstrated in clinical trials of chronic brain ischemia and Parkinson’s disease.
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Cite this article as:
Boldyrev Alexander, Bryushkova Ekaterina, Mashkina Anna and Vladychenskaya Elizaveta, Why Is Homocysteine Toxic for the Nervous and Immune Systems?, Current Aging Science 2013; 6 (1) . https://dx.doi.org/10.2174/18746098112059990007
DOI https://dx.doi.org/10.2174/18746098112059990007 |
Print ISSN 1874-6098 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-6128 |
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