title: Lysine acetyltransferases CBP and p300 as therapeutic targets in cognitive and neurodegenerative disorders.
abstract: Neuropsychiatric pathologies, including neurodegenerative diseases and neurodevelopmental syndromes, are frequently associated with dysregulation of various essential cellular mechanisms, such as transcription, mitochondrial respiration and protein degradation. In these complex scenarios, it is difficult to pinpoint the specific molecular dysfunction that initiated the pathology or that led to the fatal cascade of events that ends with the death of the neuron. Among the possible original factors, epigenetic dysregulation has attracted special attention. This review focuses on two highly related epigenetic factors that are directly involved in a number of neurological disorders, the lysine acetyltransferases CREB-binding protein (CBP) and E1A-associated protein p300 (p300). We first comment on the role of chromatin acetylation and the enzymes that control it, particularly CBP and p300, in neuronal plasticity and cognition. Next, we describe the involvement of these proteins in intellectual disability and in different neurodegenerative diseases. Finally, we discuss the potential of ameliorative strategies targeting CBP/p300 for the treatment of these disorders.
authors: Instituto de Neurociencias, Av. Santiago Ramon y Cajal s/n. Sant Joan d'Alacant 03550, Alicante, Spain.
authors: Luis M
authors: LM
authors: Valor
authors: Jose
authors: J
authors: Viosca
authors: Jose P
authors: JP
authors: Lopez-Atalaya
authors: Angel
authors: A
authors: Barco
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000123:Acetyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D018697:Nootropic Agents / Q000627:therapeutic use; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; D009419:Nerve Tissue Proteins; D018697:Nootropic Agents; D000123:Acetyltransferases; C084723:acetyl-CoA - lysine N6-acetyltransferase; D051548:Histone Acetyltransferases; D050880:p300-CBP Transcription Factors; D006655:Histone Deacetylases