title: Acetyltransferases (HATs) as targets for neurological therapeutics.
abstract: 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.
authors.affiliation: Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR7364, Université de Strasbourg-CNRS, GDR CNRS 2905, Faculté de Psychologie, 12 rue Goethe, 67000, Strasbourg, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Schneider
authors.forename: Snehajyoti
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Olivier
authors.initials: O
authors.lastname: Bousiges
authors.forename: B Ruthrotha
authors.initials: BR
authors.lastname: Selvi
authors.forename: Amrutha
authors.initials: A
authors.lastname: Swaminathan
authors.forename: Raphaelle
authors.initials: R
authors.lastname: Cassel
authors.forename: Frédéric
authors.initials: F
authors.lastname: Blanc
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Kundu
authors.forename: Anne-Laurence
authors.initials: AL
authors.lastname: Boutillier
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D009474:Neurons / Q000378:metabolism*
chemical_list: D006657:Histones; D000123:Acetyltransferases; D051548:Histone Acetyltransferases