A model for inhibition of kindling progression by 2DG.
(a) Under normal circumstances, NADH generated by glycolysis destabilizes the interaction of CtBP and NRSF, allowing transcription of NRSF target genes such as BDNF and TrkB and maintaining normal neuronal excitability. (b) Administration of 2DG inhibits glycolysis, reducing NADH concentrations. The co-repressor CtBP is recruited to form the NRSF:CtBP complex on NRSF target genes, reducing their transcription. Lower expression of BDNF and TrkB leads to reduced neuronal excitability, increasing seizure threshold and inhibiting progression of kindling.
生物谷報(bào)道：目前，研究人員研制出一種抑制小鼠癲癇發(fā)作的嶄新方法,，新結(jié)果顯示糖酵解抑制劑有望成為癲癇治療的新戰(zhàn)略,，這一最新研究報(bào)告發(fā)表在11月號(hào)的《自然—神經(jīng)科學(xué)》上。
癲癇會(huì)侵襲世界上大約有1%的人口,。然而,，現(xiàn)有藥物無(wú)法控制其中1/3患者的病情發(fā)作。一個(gè)事實(shí)讓Garriga-Canut和同事深受啟發(fā)：部分癲癇患者的病情因一種完全避免糖類(lèi)的特制飲食而大有好轉(zhuǎn),。這種特制配方的飲食名為生酮飲食,，它是指高脂肪、低蛋白質(zhì)和碳水化合物的一種飲食,，數(shù)十年來(lái)主要用于治療兒童難治性癲癇,，臨床療效確切，副反應(yīng)小,，但其作用機(jī)制至今尚不清楚,。
糖酵解是一種分解碳水化合物的過(guò)程，在癲癇患者體內(nèi)這個(gè)過(guò)程被特定飲食抑制了,。Garriga-Canut和同事用含糖酵解抑制劑2-脫氧-D-葡萄糖（2DG）的飲食治療癲癇小鼠,，結(jié)果發(fā)現(xiàn)小鼠發(fā)生癲癇的次數(shù)和嚴(yán)重程度大大降低了。
Garriga-Canut和同事推測(cè),，也許是糖酵解終端產(chǎn)物中的某一種物質(zhì)增強(qiáng)了神經(jīng)細(xì)胞的活性,，因而抑制糖酵解可能會(huì)降低神經(jīng)細(xì)胞的活性和癲癇發(fā)作的可能性。他們發(fā)現(xiàn)一種名為NADH的糖酵解產(chǎn)物可在轉(zhuǎn)錄因子NRSF的協(xié)助下與活性升高的CtBP結(jié)合,，產(chǎn)生抑制癲癇的染色質(zhì)環(huán)境,，阻止糖酵解會(huì)降低這些基因的表達(dá)。
原文：
Nature Neuroscience - 9, 1382 - 1387 (2006)
2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP–dependent metabolic regulation of chromatin structure
Mireia Garriga-Canut & Avtar Roopra etal
Abstract | Full text | PDF (208K) | Supplementary Information
相關(guān)文獻(xiàn)：
Nature Neuroscience - 9, 1351 - 1352 (2006)
Inhibiting glycolysis to reduce seizures: how it might work
Yang Zhong Huang & James O McNamara
Abstract | Full text | PDF (163K)
相關(guān)基因 pubmed gene：
CtBP
C-terminal Binding Protein [Drosophila melanogaster]
Other Aliases: Dmel_CG7583, 0256/16, 256/16, CG7583, EP(3)3528, G9, RE01030, RE61183, ctbp, dCtBP, l(3)G9
Other Designations: C-terminal Binding Protein CG7583-PA, isoform A; C-terminal Binding Protein CG7583-PB, isoform B; C-terminal Binding Protein CG7583-PC, isoform C; C-terminal Binding Protein CG7583-PD, isoform D; C-terminal Binding Protein CG7583-PE, isoform E
Chromosome: 3R; Location: 87D8-87D9
GeneID: 41602
