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Metabolic Regulation of Chromatin Structure During Epilepsy: Therapeutic Implications.
Author(s) -
Roopra Avtar S
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.408.2
Subject(s) - ketogenic diet , epileptogenesis , epilepsy , anticonvulsant , chromatin , cell metabolism , biology , neuroscience , endocrinology , metabolism , gene , biochemistry
Energy supply is critical for essential functions in all cells. There is increasing evidence that dietary carbohydrate and caloric restriction moderate cellular responses to damage, alter ageing processes, enhance longevity and may have therapeutic affects in neurological disorders such as epilepsy, Alzheimer's Disease and Huntington's Chorea. Dietary regimes termed ‘ketogenic diets’ which iso‐calorically replaces carbohydrates with fats and protein, can produce significant anticonvulsant effects in patients with epilepsy and have successfully been used therapeutically. The mechanisms behind the beneficial effects of ‘ketogenic diets’ are completely unknown. We show that neuronal genes heavily implicated in epileptogenesis are directly and chronically controlled by cellular metabolism due to regulated recruitment of a metabolism‐sensing chromatin modifying complex to their promoters in vivo. We propose that these mechanisms may underlie the beneficial effects of ‘ketogenic diets’ in epilepsy. Our model has allowed the prediction and validation of a small molecule regulator of energy metabolism to potently inhibit epileptogenesis in animal models with no detected adverse side effects.