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- Title
2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure.
- Authors
Garriga-Canut, Mireia; Schoenike, Barry; Qazi, Romena; Bergendahl, Karen; Daley, Timothy J; Pfender, Rebecca M; Morrison, John F; Ockuly, Jeffrey; Stafstrom, Carl; Sutula, Thomas; Roopra, Avtar
- Abstract
Temporal lobe epilepsy is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the 'ketogenic diet'. Here we have investigated the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in the rat kindling model of temporal lobe epilepsy. We show that 2DG potently reduces the progression of kindling and blocks seizure-induced increases in the expression of brain-derived neurotrophic factor and its receptor, TrkB. This reduced expression is mediated by the transcription factor NRSF, which recruits the NADH-binding co-repressor CtBP to generate a repressive chromatin environment around the BDNF promoter. Our results show that 2DG has anticonvulsant and antiepileptic properties, suggesting that anti-glycolytic compounds may represent a new class of drugs for treating epilepsy. The metabolic regulation of neuronal genes by CtBP will open avenues of therapy for neurological disorders and cancer.
- Publication
Nature neuroscience, 2006, Vol 9, Issue 11, p1382
- ISSN
1097-6256
- Publication type
Journal Article
- DOI
10.1038/nn1791