Journal
NEUROTHERAPEUTICS
Volume 10, Issue 4, Pages 568-588Publisher
SPRINGER
DOI: 10.1007/s13311-013-0204-7
Keywords
HAT activator molecule; Lysine acetylation; CREB-binding protein; Learning and memory; Adult neurogenesis; Neurodegenerative diseases
Funding
- Centre National de la Recherche Scientifique (CNRS)
- University of Strasbourg
- Department of Biotechnology
- Government of India [DBT/CSH/GIA/1752]
- Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR)
- Agence Nationale de la Recherche [ANR-12-MALZ-0002-01]
- Indo-French Centre for the Promotion of Advanced Research (IFCPAR/CEFIPRA) [4803-3]
- Alsace Alzheimer 67 association
- Department of Science and Technology through the government of India
- French government
- Agence Nationale pour la Recherche [ANR-12-MALZ-0002]
- Novartis
- Lundbeck
- Bayer Schering
- Merck Serono
- TEVA Neurosciences
- Pfizer
- Council for Scientific and Industrial Research
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The acetylation of histone and non-histone proteins controls a great deal of cellular functions, thereby affecting the entire organism, including the brain. Acetylation modifications are mediated through histone acetyltransferases (HAT) and deacetylases (HDAC), and the balance of these enzymes regulates neuronal homeostasis, maintaining the pre-existing acetyl marks responsible for the global chromatin structure, as well as regulating specific dynamic acetyl marks that respond to changes and facilitate neurons to encode and strengthen long-term events in the brain circuitry (e. g., memory formation). Unfortunately, the dysfunction of these finely-tuned regulations might lead to pathological conditions, and the deregulation of the HAT/HDAC balance has been implicated in neurological disorders. During the last decade, research has focused on HDAC inhibitors that induce a histone hyperacetylated state to compensate acetylation deficits. The use of these inhibitors as a therapeutic option was efficient in several animal models of neurological disorders. The elaboration of new cell-permeant HAT activators opens a new era of research on acetylation regulation. Although pathological animal models have not been tested yet, HAT activator molecules have already proven to be beneficial in ameliorating brain functions associated with learning and memory, and adult neurogenesis in wild-type animals. Thus, HAT activator molecules contribute to an exciting area of research.
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