Neural tube defects and folate: case far from closed

Nat Rev Neurosci. 2006 Sep;7(9):724-31. doi: 10.1038/nrn1986.


Neural tube closure takes place during early embryogenesis and requires interactions between genetic and environmental factors. Failure of neural tube closure is a common congenital malformation that results in morbidity and mortality. A major clinical achievement has been the use of periconceptional folic acid supplements, which prevents approximately 50-75% of cases of neural tube defects. However, the mechanism underlying the beneficial effects of folic acid is far from clear. Biochemical, genetic and epidemiological observations have led to the development of the methylation hypothesis, which suggests that folic acid prevents neural tube defects by stimulating cellular methylation reactions. Exploring the methylation hypothesis could direct us towards additional strategies to prevent neural tube defects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Central Nervous System / abnormalities*
  • Central Nervous System / metabolism*
  • Central Nervous System / physiopathology
  • Folic Acid / metabolism*
  • Folic Acid / therapeutic use
  • Folic Acid Deficiency / complications*
  • Folic Acid Deficiency / physiopathology
  • Folic Acid Deficiency / prevention & control
  • Genetic Predisposition to Disease / genetics
  • Homocysteine / metabolism
  • Humans
  • Methionine / biosynthesis
  • Methylation / drug effects
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
  • Neural Tube Defects / etiology*
  • Neural Tube Defects / physiopathology*
  • Neural Tube Defects / prevention & control


  • Homocysteine
  • Folic Acid
  • Methionine
  • Methylenetetrahydrofolate Reductase (NADPH2)