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The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease
TLDR
We demonstrate that this “Connectivity Map” resource can be used to find connections among small molecules sharing a mechanism of action, chemicals and physiological processes, and diseases and drugs. Expand
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HDAC2 negatively regulates memory formation and synaptic plasticity
Chromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis)Expand
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Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation
Protein acetylation, especially histone acetylation, is the subject of both research and clinical investigation. At least four small-molecule histone deacetylase inhibitors are currently in clinicalExpand
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Disrupted in Schizophrenia 1 Regulates Neuronal Progenitor Proliferation via Modulation of GSK3β/β-Catenin Signaling
The Disrupted in Schizophrenia 1 (DISC1) gene is disrupted by a balanced chromosomal translocation (1; 11) (q42; q14.3) in a Scottish family with a high incidence of major depression, schizophrenia,Expand
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Chemical Phylogenetics of Histone Deacetylases
The broad study of histone deacetylases in chemistry, biology and medicine relies on tool compounds to derive mechanistic insights. A phylogenetic analysis of Class I and II HDACs as targets of aExpand
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A polygenic burden of rare disruptive mutations in schizophrenia
Schizophrenia is a common disease with a complex aetiology, probably involving multiple and heterogeneous genetic factors. Here, by analysing the exome sequences of 2,536 schizophrenia cases andExpand
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An epigenetic blockade of cognitive functions in the neurodegenerating brain
Cognitive decline is a debilitating feature of most neurodegenerative diseases of the central nervous system, including Alzheimer’s disease. The causes leading to such impairment are only poorlyExpand
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Histone Deacetylase 5 Epigenetically Controls Behavioral Adaptations to Chronic Emotional Stimuli
Previous work has identified alterations in histone acetylation in animal models of drug addiction and depression. However, the mechanisms which integrate drugs and stress with changes in chromatinExpand
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Inhibitors of Class 1 Histone Deacetylases Reverse Contextual Memory Deficits in a Mouse Model of Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by cognitive impairments that progress to dementia and death. The earliest symptoms of AD present as a relativelyExpand
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Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation
Behavioral Profiling The complexity of the brain makes it difficult to predict how a drug will affect behavior without direct testing in live animals. Rihel et al. (p. 348) developed aExpand
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