Toxicity induced by a polyglutamated folate analog is attenuated by NAALADase inhibition
Folates have been shown to be neurotoxic and convulsive. Endogenously, folates exist in the brain in a polyglutamated form with 1–7 terminal glutamates (approx. 1 μM). The brain enzyme N-acetylated alpha-linked acidic dipeptidase (NAALADase) has been shown to remove sequentially the gamma-linked glu...
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Published in | Brain research Vol. 843; no. 1; pp. 48 - 52 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
London
Elsevier B.V
02.10.1999
Amsterdam Elsevier New York, NY |
Subjects | |
Online Access | Get full text |
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Summary: | Folates have been shown to be neurotoxic and convulsive. Endogenously, folates exist in the brain in a polyglutamated form with 1–7 terminal glutamates (approx. 1 μM). The brain enzyme
N-acetylated alpha-linked acidic dipeptidase (NAALADase) has been shown to remove sequentially the gamma-linked glutamates from folic acid polyglutamates. We report that, at high concentrations (300 μM–30 mM), a folic acid hexaglutamate analog is dose-dependently toxic to dissociated rat cortical cultures and that this toxicity is reversed by 2-PMPA, a potent and selective NAALADase inhibitor. These data suggest a new mechanism for folic acid toxicity. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0006-8993 1872-6240 |
DOI: | 10.1016/S0006-8993(99)01879-X |