Neural tube defects and folate: case far from closed

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Abstract
Neural tube closure is a highly complex process that occurs during embryogenesis. Failure of the neural tube to close can lead to neural tube defects (NTDs) such as anencephaly and spina bifida. Periconceptional use of folic acid supplements prevents about a half to three-quarters of cases of NTDs. The main function of the metabolism of the vitamin folate is to transport one-carbon units, which are used in the synthesis of DNA building blocks (purines and thymidine) and for methylation of numerous compounds, including DNA, RNA, proteins and lipids. A variant of the gene methylenetetrahydrofolate reductase (MTHFR) is the first genetic risk factor to be identified for NTDs. This role goes some way to explaining the prevention of NTDs by folic acid, a precursor of the natural substrate of MTHFR. Knowledge of folate metabolism and the biochemical role of MTHFR has led to the development of the methylation hypothesis for NTDs, which suggests that reduced cellular methylation hampers neural tube closure. If folic acid prevents NTDs through improved methylation, new therapeutic strategies, such as the administration of agents involved in donating a methyl group, for example, riboflavin, vitamin B12, methionine and choline, must be explored.