TY  - JOUR
AU  - Benito, E.
AU  - Ramachandran, B.
AU  - Schroeder, H.
AU  - Schmidt, G.
AU  - Urbanke, H.
AU  - Burkhardt, S.
AU  - Capece, V.
AU  - Dean, C.
AU  - Fischer, A.
TI  - The BET/BRD inhibitor JQ1 improves brain plasticity in WT and APP mice.
JO  - Translational Psychiatry
VL  - 7
IS  - 9
SN  - 2158-3188
CY  - London
PB  - Nature Publishing Group
M1  - DZNE-2020-05851
SP  - e1239
PY  - 2017
AB  - Histone 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.
KW  - Alzheimer Disease: genetics
KW  - Amyloid beta-Protein Precursor: genetics
KW  - Animals
KW  - Azepines: administration & dosage
KW  - Behavior, Animal: drug effects
KW  - Chromosomal Proteins, Non-Histone: antagonists & inhibitors
KW  - Gene Expression: drug effects
KW  - Hippocampus: drug effects
KW  - Hippocampus: metabolism
KW  - Hippocampus: physiology
KW  - Long-Term Potentiation: drug effects
KW  - Male
KW  - Memory: drug effects
KW  - Memory: physiology
KW  - Mice, Inbred C57BL
KW  - Mice, Transgenic
KW  - Nuclear Proteins: antagonists & inhibitors
KW  - Transcription Factors: antagonists & inhibitors
KW  - Triazoles: administration & dosage
KW  - (+)-JQ1 compound (NLM Chemicals)
KW  - Amyloid beta-Protein Precursor (NLM Chemicals)
KW  - Azepines (NLM Chemicals)
KW  - BRDT protein, mouse (NLM Chemicals)
KW  - Brd2 protein, mouse (NLM Chemicals)
KW  - Brd3 protein, mouse (NLM Chemicals)
KW  - Brd4 protein, mouse (NLM Chemicals)
KW  - Chromosomal Proteins, Non-Histone (NLM Chemicals)
KW  - Nuclear Proteins (NLM Chemicals)
KW  - Transcription Factors (NLM Chemicals)
KW  - Triazoles (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:28949335
C2  - pmc:PMC5639246
DO  - DOI:10.1038/tp.2017.202
UR  - https://pub.dzne.de/record/139529
ER  -