Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders.
Epigenetic chromatin remodeling and modifications of DNA represent central mechanisms for regulation of gene expression during brain development and in memory formation. Emerging evidence implicates epigenetic modifications in disorders of synaptic plasticity and cognition. This review focuses on recent findings that HDAC inhibitors can ameliorate deficits in synaptic plasticity, cognition, and stress-related behaviors in a wide range of neurologic and psychiatric disorders including Huntington's disease, Parkinson's disease, anxiety and mood disorders, Rubinstein-Taybi syndrome, and Rett syndrome. These agents may prove useful in the clinic for the treatment of the cognitive impairments that are central elements of many neurodevelopmental, neurological, and psychiatric disorders.
Abel
Ted
T
Department of Biology, University of Pennsylvania, 204G Lynch Laboratories, 433 South University Avenue, Philadelphia, PA 19104-6018, USA. abele@sas.upenn.edu
Zukin
R Suzanne
RS
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D001008:Anxiety Disorders / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy*; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D010300:Parkinson Disease / Q000188:drug therapy; D012559:Schizophrenia / Q000188:drug therapy; D020521:Stroke / Q000188:drug therapy
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones