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000139529 0247_ $$2doi$$a10.1038/tp.2017.202
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000139529 041__ $$aEnglish
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000139529 1001_ $$0P:(DE-2719)2810482$$aBenito, E.$$b0$$eFirst author$$udzne
000139529 245__ $$aThe BET/BRD inhibitor JQ1 improves brain plasticity in WT and APP mice.
000139529 260__ $$aLondon$$bNature Publishing Group$$c2017
000139529 264_1 $$2Crossref$$3online$$bSpringer Science and Business Media LLC$$c2017-09-26
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000139529 520__ $$aHistone acetylation is essential for memory formation and its deregulation contributes to the pathogenesis of Alzheimer's disease. Thus, targeting histone acetylation is discussed as a novel approach to treat dementia. The histone acetylation landscape is shaped by chromatin writer and eraser proteins, while readers link chromatin state to cellular function. Chromatin readers emerged novel drug targets in cancer research but little is known about the manipulation of readers in the adult brain. Here we tested the effect of JQ1-a small-molecule inhibitor of the chromatin readers BRD2, BRD3, BRD4 and BRDT-on brain function and show that JQ1 is able to enhance cognitive performance and long-term potentiation in wild-type animals and in a mouse model for Alzheimer's disease. Systemic administration of JQ1 elicited a hippocampal gene expression program that is associated with ion channel activity, transcription and DNA repair. Our findings suggest that JQ1 could be used as a therapy against dementia and should be further tested in the context of learning and memory.
000139529 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000139529 542__ $$2Crossref$$i2017-09-01$$uhttps://creativecommons.org/licenses/by/4.0
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000139529 650_7 $$2NLM Chemicals$$a(+)-JQ1 compound
000139529 650_7 $$2NLM Chemicals$$aAmyloid beta-Protein Precursor
000139529 650_7 $$2NLM Chemicals$$aAzepines
000139529 650_7 $$2NLM Chemicals$$aBRDT protein, mouse
000139529 650_7 $$2NLM Chemicals$$aBrd2 protein, mouse
000139529 650_7 $$2NLM Chemicals$$aBrd3 protein, mouse
000139529 650_7 $$2NLM Chemicals$$aBrd4 protein, mouse
000139529 650_7 $$2NLM Chemicals$$aChromosomal Proteins, Non-Histone
000139529 650_7 $$2NLM Chemicals$$aNuclear Proteins
000139529 650_7 $$2NLM Chemicals$$aTranscription Factors
000139529 650_7 $$2NLM Chemicals$$aTriazoles
000139529 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000139529 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: genetics
000139529 650_2 $$2MeSH$$aAnimals
000139529 650_2 $$2MeSH$$aAzepines: administration & dosage
000139529 650_2 $$2MeSH$$aBehavior, Animal: drug effects
000139529 650_2 $$2MeSH$$aChromosomal Proteins, Non-Histone: antagonists & inhibitors
000139529 650_2 $$2MeSH$$aGene Expression: drug effects
000139529 650_2 $$2MeSH$$aHippocampus: drug effects
000139529 650_2 $$2MeSH$$aHippocampus: metabolism
000139529 650_2 $$2MeSH$$aHippocampus: physiology
000139529 650_2 $$2MeSH$$aLong-Term Potentiation: drug effects
000139529 650_2 $$2MeSH$$aMale
000139529 650_2 $$2MeSH$$aMemory: drug effects
000139529 650_2 $$2MeSH$$aMemory: physiology
000139529 650_2 $$2MeSH$$aMice, Inbred C57BL
000139529 650_2 $$2MeSH$$aMice, Transgenic
000139529 650_2 $$2MeSH$$aNuclear Proteins: antagonists & inhibitors
000139529 650_2 $$2MeSH$$aTranscription Factors: antagonists & inhibitors
000139529 650_2 $$2MeSH$$aTriazoles: administration & dosage
000139529 7001_ $$0P:(DE-HGF)0$$aRamachandran, B.$$b1
000139529 7001_ $$0P:(DE-2719)2812036$$aSchroeder, H.$$b2$$udzne
000139529 7001_ $$0P:(DE-HGF)0$$aSchmidt, G.$$b3
000139529 7001_ $$0P:(DE-2719)2811034$$aUrbanke, H.$$b4$$udzne
000139529 7001_ $$0P:(DE-2719)2810773$$aBurkhardt, S.$$b5$$udzne
000139529 7001_ $$0P:(DE-2719)2810626$$aCapece, V.$$b6$$udzne
000139529 7001_ $$0P:(DE-HGF)0$$aDean, C.$$b7
000139529 7001_ $$0P:(DE-2719)2000047$$aFischer, A.$$b8$$eLast author$$udzne
000139529 77318 $$2Crossref$$3journal-article$$a10.1038/tp.2017.202$$b : Springer Science and Business Media LLC, 2017-09-01$$n9$$pe1239-e1239$$tTranslational Psychiatry$$v7$$x2158-3188$$y2017
000139529 773__ $$0PERI:(DE-600)2609311-X$$a10.1038/tp.2017.202$$gVol. 7, no. 9, p. e1239 - e1239$$n9$$pe1239$$q7:9<e1239 - e1239$$tTranslational Psychiatry$$v7$$x2158-3188$$y2017
000139529 8564_ $$uhttps://pub.dzne.de/record/139529/files/DZNE-2020-05851.pdf$$yOpenAccess
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000139529 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639246
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