| abstract |
The canonical Wnt signaling pathway is implicated in many disorders including neural tube defects, limb malformations, and heart defects, developmental disorders associated with alcohol exposure (fetal alcohol syndrome) or exposure to bipolar medications (i.e. lithium), wound healing, and Alzheimer's disease. Elevated plasma homocysteine (HCy), which results from folate (folic acid, FA) deficiency, the mood-stabilizing drug lithium (Li), and alcohol (ethanol) are linked to the induction of human congenital heart and neural tube defects. FA supplementation ameliorates the observed developmental errors in the Li- HCy, or alcohol-exposed mouse embryos and normalized heart function. Li, HCy or Wnt3A suppress Wnt-modulated Hex and Islet-1 expression. FA protects from the gene misexpression that is induced by all three factors. Administration of myo-inositol with FA synergistically enhances the protective effect. |