title: Histone deacetylases in memory and cognition.
abstract: Over the past 30 years, lysine acetylation of histone and nonhistone proteins has become established as a key modulator of gene expression regulating numerous aspects of cell biology. Neuronal growth and plasticity are no exception; roles for lysine acetylation and deacetylation in brain function and dysfunction continue to be uncovered. Transcriptional programs coupling synaptic activity to changes in gene expression are critical to the plasticity mechanisms underlying higher brain functions. These transcriptional programs can be modulated by changes in histone acetylation, and in many cases, transcription factors and histone-modifying enzymes are recruited together to plasticity-associated genes. Lysine acetylation, catalyzed by lysine acetyltransferases (KATs), generally promotes cognitive performance, whereas the opposing process, catalyzed by histone lysine deacetylases (HDACs), appears to negatively regulate cognition in multiple brain regions. Consistently, mutation or deregulation of different KATs or HDACs contributes to neurological dysfunction and neurodegeneration. HDAC inhibitors have shown promise as a treatment to combat the cognitive decline associated with aging and neurodegenerative disease, as well as to ameliorate the symptoms of depression and posttraumatic stress disorder, among others. In this review, we discuss the evidence for the roles of HDACs in cognitive function as well as in neurological disorders and disease. In particular, we focus on HDAC2, which plays a central role in coupling lysine acetylation to synaptic plasticity and mediates many of the effects of HDAC inhibition in cognition and disease.
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Penney
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. lhtsai@mit.edu.
authors.forename: Li-Huei
authors.initials: LH
authors.lastname: Tsai
mesh_terms: D000107:Acetylation; D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D003071:Cognition; D003863:Depression / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D008568:Memory; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology
chemical_list: D056572:Histone Deacetylase Inhibitors; D051548:Histone Acetyltransferases; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2