Epigenetic Treatments for Cognitive Impairments

被引:82
作者
Day, Jeremy J. [1 ,2 ]
Sweatt, J. David [1 ,2 ]
机构
[1] Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL 35294 USA
[2] Univ Alabama Birmingham, Evelyn F McKnight Brain Inst, Birmingham, AL 35294 USA
关键词
learning and memory; neurodegeneration; neuroprotection; drug discovery; development; epigenetics; HISTONE DEACETYLASE INHIBITORS; LONG-TERM-MEMORY; ORIGIN ALLELIC EXPRESSION; RUBINSTEIN-TAYBI-SYNDROME; LOCAL PROTEIN-SYNTHESIS; DNA METHYLATION; MOUSE MODEL; REGULATES MEMORY; RETT-SYNDROME; SYNAPTIC PLASTICITY;
D O I
10.1038/npp.2011.85
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
Epigenetic mechanisms integrate signals from diverse intracellular transduction cascades and in turn regulate genetic readout. Accumulating evidence has revealed that these mechanisms are critical components of ongoing physiology and function in the adult nervous system, and are essential for many cognitive processes, including learning and memory. Moreover, a number of psychiatric disorders and syndromes that involve cognitive impairments are associated with altered epigenetic function. In this review, we will examine how epigenetic mechanisms contribute to cognition, consider how changes in these mechanisms may lead to cognitive impairments in a range of disorders and discuss the potential utility of therapeutic treatments that target epigenetic machinery. Finally, we will comment on a number of caveats associated with interpreting epigenetic changes and using epigenetic treatments, and suggest future directions for research in this area that will expand our understanding of the epigenetic changes underlying cognitive disorders. Neuropsychopharmacology Reviews (2012) 37, 247-260; doi: 10.1038/npp.2011.85; published online 18 May 2011
引用
收藏
页码:247 / 260
页数:14
相关论文
共 154 条
[1]
Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders [J].
Abe, Ted ;
Zukin, R. Suzanne .
CURRENT OPINION IN PHARMACOLOGY, 2008, 8 (01) :57-64
[2]
MeCP2-Mediated Transcription Repression in the Basolateral Amygdala May Underlie Heightened Anxiety in a Mouse Model of Rett Syndrome [J].
Adachi, Megumi ;
Autry, Anita E. ;
Covington, Herb E., III ;
Monteggia, Lisa M. .
JOURNAL OF NEUROSCIENCE, 2009, 29 (13) :4218-4227
[3]
A novel mutation in JARID1C/SMCX in a patient with autism spectrum disorder (ASD) [J].
Adegbola, Abidemi ;
Gao, Hanlin ;
Sommer, Steve ;
Browning, Marsha .
AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2008, 146A (04) :505-511
[4]
Epigenetic Regulation in Human Brain-Focus on Histone Lysine Methylation [J].
Akbarian, Schahram ;
Huang, Hsien-Sung .
BIOLOGICAL PSYCHIATRY, 2009, 65 (03) :198-203
[5]
Chromatin acetylation, memory, and LTP are impaired in CBP+/- mice:: A model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration [J].
Alarcón, JM ;
Malleret, G ;
Touzani, K ;
Vronskaya, S ;
Ishii, S ;
Kandel, ER ;
Barco, A .
NEURON, 2004, 42 (06) :947-959
[6]
The role of protein synthesis during the labile phases of memory: Revisiting the skepticism [J].
Alberini, Cristina M. .
NEUROBIOLOGY OF LEARNING AND MEMORY, 2008, 89 (03) :234-246
[7]
Amir RE, 2000, AM J MED GENET, V97, P147, DOI 10.1002/1096-8628(200022)97:2<147::AID-AJMG6>3.0.CO
[8]
2-O
[9]
Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2 [J].
Amir, RE ;
Van den Veyver, IB ;
Wan, M ;
Tran, CQ ;
Francke, U ;
Zoghbi, HY .
NATURE GENETICS, 1999, 23 (02) :185-188
[10]
[Anonymous], 1996, EPIGENETIC MECH GENE