2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure.

2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Research Abstract Details 

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2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Abstract Text:

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.

2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Publishing Authors By Initials

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2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Nature neuroscience

VOLUME: 9

Page Numbers: 1382-7

Journal Abbreviation: Nat. Neurosci.

ISSN: 1097-6256

DAY: 15

MONTH: 10

YEAR: 2006

2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Information

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LANGUAGE: eng

NlmUniqueID: 9809671

2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Keywords Mesh Terms:

KEYWORDS: Transcription Factors

MESH TERMS: physiology

Chemical & Substance for Abstract: 2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Information

Substance Name: Receptor, trkB

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for 2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure.

AFFILIATION: Department of Neurology, Medical Science Center, Room 1715, University of Wisconsin-Madison, 1300 University Avenue, Madison, Wisconsin 53706, USA.

Country: United States

AGENCY: United States PHS

GRANT: R01 25020

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MEDLINETA: Nat Neurosci

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