Neurotoxicity of folates: implications for vitamin B12 deficiency and Huntington's chorea.
Recent work has shown that several folates interact with excitatory kainic acid receptors in the mammalian brain and appear to have agonist activity at these receptors. Since kainic acid is a potent neurotoxin it is possible that folates share this toxicity  and that high levels of folates result in neuronal damage. Levels of methyltetrahydrofolate are markedly elevated in vitamin B12 deficiency, a disease associated with neuronal destruction. We propose that this destruction occurs as a result of a neurotoxic action of methyltetrahydrofolate. Injection of kainic acid into the basal ganglia of experimental animals produces a pattern of damage similar to that found in patients dying of Huntington's chorea. It is possible that the underlying defect in this disease resides in the pathways of folate metabolism such that a neurotoxic excess of folates accumulates in the central nervous system. Such a disease process might be arrested by antifolate drugs.
D000818:Animals; D001921:Brain / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D002685:Chiroptera; D005492:Folic Acid / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D007608:Kainic Acid / Q000378:metabolism / Q000633:toxicity; D008954:Models, Biological; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D018092:Kainic Acid Receptors; D013763:Tetrahydrofolates / Q000378:metabolism* / Q000633:toxicity; D014806:Vitamin B 12 Deficiency / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005492:Folic Acid; D007608:Kainic Acid; D011956:Receptors, Cell Surface; D018092:Kainic Acid Receptors; D013763:Tetrahydrofolates; D005680:gamma-Aminobutyric Acid; C005984:5-methyltetrahydrofolate