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Folate one-carbon metabolism and neural development

Folate one-carbon metabolism (FOCM) comprises a set of cellular reactions that transfer one-carbon units for a number of downstream functions including nucleotide biosynthesis and methylation reactions. Use of supplemental folic acid (the synthetic form of folate) before and during early pregnancy can prevent NTDs and all women planning pregnancy are recommended to take a folic acid supplement. These findings implicate folate metabolism in neural tube closure and a major focus of our research is to understand the relationship between folate status and susceptibility to NTDs.

In previous work we:


CURRENT WORK INCLUDES:

  • Studies to determine how loss of function of glycine decarboxylase (Gldc) causes NTDs.
  • Evaluating possible approaches for the prevention of folic acid-resistant NTDs. For example, we found that treatment with nucleotides (one of the products of folate metabolism) can prevent spina bifida in a folic acid-resistant mouse model (Leung KY et al, Brain 2013).
  • Investigating the requirement for folate-dependent methylation in neural tube closure, using mass spectrometry-based metabolite analysis and epigenetic studies.

Analysis of folate metabolism in additional disease models and during normal development

As well as NTDs, abnormal FOCM is implicated in a number of other diseases including various cancers, fatty liver disease, inborn errors of metabolism, autism and age-related cognitive impairment.