Lysine Acetyltransferases CBP and p300 as Therapeutic Targets in Cognitive and Neurodegenerative Disorders
Luis M. Valor, Jose Viosca, Jose P. Lopez-Atalaya and Angel Barco
Affiliation: Instituto de Neurociencias (Universidad Miguel Hernandez – Consejo Superior de Investigaciones Cientificas), Av. Santiago Ramon y Cajal s/n. Sant Joan d’Alacant 03550, Alicante, Spain.
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.
Keywords: Histone acetylation, CBP, p300, Rubinstein-Taybi syndrome, Huntington’s disease, Alzheimer’s disease, HDACi, KATe, KATi.
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