Epilepsy treatment. Targeting LDH enzymes with a stiripentol analog to treat epilepsy.
Science
; 347(6228): 1362-7, 2015 Mar 20.
Article
en En
| MEDLINE
| ID: mdl-25792327
ABSTRACT
Neuronal excitation is regulated by energy metabolism, and drug-resistant epilepsy can be suppressed by special diets. Here, we report that seizures and epileptiform activity are reduced by inhibition of the metabolic pathway via lactate dehydrogenase (LDH), a component of the astrocyte-neuron lactate shuttle. Inhibition of the enzyme LDH hyperpolarized neurons, which was reversed by the downstream metabolite pyruvate. LDH inhibition also suppressed seizures in vivo in a mouse model of epilepsy. We further found that stiripentol, a clinically used antiepileptic drug, is an LDH inhibitor. By modifying its chemical structure, we identified a previously unknown LDH inhibitor, which potently suppressed seizures in vivo. We conclude that LDH inhibitors are a promising new group of antiepileptic drugs.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Safrol
/
Convulsiones
/
Dioxolanos
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Inhibidores Enzimáticos
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L-Lactato Deshidrogenasa
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Anticonvulsivantes
Límite:
Animals
Idioma:
En
Revista:
Science
Año:
2015
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA