Epigenetic dysregulation in cognitive disorders.
Epigenetic mechanisms are not only essential for biological functions requiring stable molecular changes such as the establishment of cell identity and tissue formation, they also constitute dynamic intracellular processes for translating environmental stimuli into modifications in gene expression. Over the past decade it has become increasingly clear that both aspects of epigenetic mechanisms play a pivotal role in complex brain functions. Evidence from patients with neurodegenerative and neurodevelopmental disorders such as Alzheimer's disease and Rett syndrome indicated that epigenetic mechanisms and chromatin remodeling need to be tightly controlled for proper cognitive functions, and their dysregulation can have devastating consequences. However, because they are dynamic, epigenetic mechanisms are also potentially reversible and may provide powerful means for pharmacological intervention. This review outlines major cognitive disorders known to be associated with epigenetic dysregulation, and discusses the potential of 'epigenetic medicine' as a promising cure.
Gräff
Johannes
J
Brain Research Institute, Medical Faculty of the University of Zürich, Zürich, Switzerland.
Mansuy
Isabelle M
IM
D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000503:physiopathology; D003072:Cognition Disorders / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic; D005600:Fragile X Syndrome / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D006657:Histones / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D015518:Rett Syndrome / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D012415:Rubinstein-Taybi Syndrome / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology
D006657:Histones