REVIEW: Molecular Mechanisms of Homocysteine Toxicity

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A. A. Boldyrev^1,2

¹Biological Faculty, Lomonosov Moscow State University, 119992 Moscow, Russia; fax: (495) 939-1376; E-mail: alexander.boldyrev@gmail.com

²Research Center of Neurology, Russian Academy of Medical Sciences, Moscow, Russia

Received September 1, 2008; Revision received November 27, 2008

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Hyperhomocysteinemia is a risk factor for a number of cardiovascular and neurodegenerative processes as well as a complicating factor in normal pregnancy. Toxic effects of homocysteine and the product of its spontaneous oxidation, homocysteic acid, are based on their ability to activate NMDA receptors, increasing intracellular levels of ionized calcium and reactive oxygen species. Even a short-term exposure of cells to homocysteic acid at concentrations characteristic of hyperhomocysteinemia induces their apoptotic transformation. The discovery of NMDA receptors both in neuronal tissue and in several other tissues and organs (including immunocompetent cells) makes them a target for toxic action of homocysteine. The neuropeptide carnosine was found to protect the organism from homocysteine toxicity. Treatment of pregnant rats with carnosine under conditions of alimentary hyperhomocysteinemia increases viability and functional activity of their progeny.

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KEY WORDS: homocysteine, homocysteic acid, NMDA receptors, neurons, lymphocytes, neutrophils

DOI: 10.1134/S0006297909060017

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