Abstract
Elevated maternal homocysteine (Hcys) is a well-established risk factor for embryonic toxicity and the development of congenital defects, particularly neural tube closure defects and neurocristopathies. The mechanisms responsible are unclear but early work has focused on the role of folate metabolism because these defects are greatly reduced by folate supplementation. As a consequence, elevated Hcys is often looked upon as being an indirect consequence of faulty folate metabolism, although more recent studies show Hcys may act directly as a teratogen. Because Hcys is at the crossroads of protein and DNA metabolism, has a propensity to chemically modify proteins directly, can generate free radicals, and even perturb ligand binding to certain receptors, the developmental processes Hcys can potentially disturb are enumerable. But in recent years, investigators have begun identifying cellular and molecular targets for the direct action of Hcys. While elevating Hcys can alter a myriad of basic cellular activities needed for normal development, our current understanding as to the specific etiological mechanisms responsible for congenital defects is very speculative. Here we provide an overview of what is currently known regarding the toxicity and teratogenicity of elevated Hcys during embryonic development, paying particular attention to neural tube and neural crest cell morphogenesis.
Keywords: homocysteine, folate, neural tube defects, neurocristopathies, congenital birth defects, neural crest, morphogenesis, teratogen, toxicity, embryo
Current Pharmaceutical Design
Title: Consequences of Elevated Homocysteine During Embryonic Development and Possible Modes of Action
Volume: 10 Issue: 22
Author(s): P. R. Brauer and B. J. Tierney
Affiliation:
Keywords: homocysteine, folate, neural tube defects, neurocristopathies, congenital birth defects, neural crest, morphogenesis, teratogen, toxicity, embryo
Abstract: Elevated maternal homocysteine (Hcys) is a well-established risk factor for embryonic toxicity and the development of congenital defects, particularly neural tube closure defects and neurocristopathies. The mechanisms responsible are unclear but early work has focused on the role of folate metabolism because these defects are greatly reduced by folate supplementation. As a consequence, elevated Hcys is often looked upon as being an indirect consequence of faulty folate metabolism, although more recent studies show Hcys may act directly as a teratogen. Because Hcys is at the crossroads of protein and DNA metabolism, has a propensity to chemically modify proteins directly, can generate free radicals, and even perturb ligand binding to certain receptors, the developmental processes Hcys can potentially disturb are enumerable. But in recent years, investigators have begun identifying cellular and molecular targets for the direct action of Hcys. While elevating Hcys can alter a myriad of basic cellular activities needed for normal development, our current understanding as to the specific etiological mechanisms responsible for congenital defects is very speculative. Here we provide an overview of what is currently known regarding the toxicity and teratogenicity of elevated Hcys during embryonic development, paying particular attention to neural tube and neural crest cell morphogenesis.
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Cite this article as:
Brauer R. P. and Tierney J. B., Consequences of Elevated Homocysteine During Embryonic Development and Possible Modes of Action, Current Pharmaceutical Design 2004; 10 (22) . https://dx.doi.org/10.2174/1381612043383692
DOI https://dx.doi.org/10.2174/1381612043383692 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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