Neural tube defects: pathogenesis and folate metabolism.
Neural tube defects (NTDs) are a group of congenital malformations with worldwide distribution and complex aetio-pathogenesis. Animal studies indicate that there may be four sites of initiation of neural tube closure (NTC). Selective involvement of these sites may lead to defects varying from anencephaly to spina bifida. The NTC involves formation of medial and dorsolateral hinge points, convergent extension and a zipper release process. Proliferation and migration of neuroectodermal cells and its morphological changes brought about by microfilaments and other cytoskeletal proteins mediate NTC. Genetic, nutritional and teratogenic mechanisms have been implicated in the pathogenesis of NTDs. Folate is an important component in one carbon metabolism that provides active moieties for synthesis of nucleic acids and proteins. Several gene defects affecting enzymes and proteins involved in transport and metabolism of folate have been associated with NTDs. It may be possible in future, to identify individuals at higher risk of NTDs by genetic studies. Epidemiological and clinical studies have shown that dietary supplementation or food fortification with folic acid would reduce the incidence of NTDs. The protective effect of folic acid may be by overcoming these metabolic blocks through unidentified mechanisms. Genetic and biochemical studies on foetal cells may supplement currently available prenatal tests to diagnose NTDs. Antiepileptic drugs (AEDs), particularly valproate and carbamazepine have been shown to increase the risk of NTDs by possibly increasing the oxidative stress and deranging the folate metabolism. Accordingly, it is recommended that all women taking AEDs may use 1-5 mg folic acid daily in the pre conception period and through pregnancy.
Pulikkunnel
Scaria T
ST
Department of Pharmacology, Medical College, Trivandrum, India.
Thomas
S V
SV
D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000378:metabolism / Q000627:therapeutic use*; D005494:Folic Acid Deficiency / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D005527:Food, Fortified; D006801:Humans; D009436:Neural Tube Defects / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D011247:Pregnancy; D012307:Risk Factors; D013763:Tetrahydrofolates / Q000172:deficiency* / Q000378:metabolism
D013763:Tetrahydrofolates; C030371:5,6,7,8-tetrahydrofolic acid; D005492:Folic Acid