The BET/BRD inhibitor JQ1 improves brain plasticity in WT and APP mice
Copyright policy )The BET/BRD inhibitor JQ1 improves brain plasticity in WT and APP mice
AbstractHistone 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.
Male, BRDT protein, mouse, Chromosomal Proteins, Non-Histone: antagonists & inhibitors, Chromosomal Proteins, Non-Histone, Long-Term Potentiation, Alzheimer Disease: genetics, Nuclear Proteins: antagonists & inhibitors, Gene Expression, Mice, Transgenic, 612, Transcription Factors: antagonists & inhibitors, Hippocampus, Hippocampus: drug effects, Amyloid beta-Protein Precursor, Bromodomain Containing Proteins, (+)-JQ1 compound, Gene Expression: drug effects, Alzheimer Disease, Memory, Memory: physiology, Animals, info:eu-repo/classification/ddc/610, Amyloid beta-Protein Precursor: genetics, Azepines: administration & dosage, Behavior, Animal, Brd4 protein, mouse, Nuclear Proteins, Azepines, Triazoles, Memory: drug effects, Mice, Inbred C57BL, Behavior, Animal: drug effects, Triazoles: administration & dosage, Hippocampus: physiology, Long-Term Potentiation: drug effects, Brd3 protein, mouse, Brd2 protein, mouse, Original Article, Hippocampus: metabolism, Transcription Factors
Male, BRDT protein, mouse, Chromosomal Proteins, Non-Histone: antagonists & inhibitors, Chromosomal Proteins, Non-Histone, Long-Term Potentiation, Alzheimer Disease: genetics, Nuclear Proteins: antagonists & inhibitors, Gene Expression, Mice, Transgenic, 612, Transcription Factors: antagonists & inhibitors, Hippocampus, Hippocampus: drug effects, Amyloid beta-Protein Precursor, Bromodomain Containing Proteins, (+)-JQ1 compound, Gene Expression: drug effects, Alzheimer Disease, Memory, Memory: physiology, Animals, info:eu-repo/classification/ddc/610, Amyloid beta-Protein Precursor: genetics, Azepines: administration & dosage, Behavior, Animal, Brd4 protein, mouse, Nuclear Proteins, Azepines, Triazoles, Memory: drug effects, Mice, Inbred C57BL, Behavior, Animal: drug effects, Triazoles: administration & dosage, Hippocampus: physiology, Long-Term Potentiation: drug effects, Brd3 protein, mouse, Brd2 protein, mouse, Original Article, Hippocampus: metabolism, Transcription Factors
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