To learn better, keep the HAT on.

Department of Psychiatry and Beiobehavioral Sciences, Neuropsychiatric Institute, University of California, Los Angeles 90095, USA.
Neuron (Impact Factor: 15.98). 07/2004; 42(6):879-81. DOI: 10.1016/j.neuron.2004.06.007
Source: PubMed

ABSTRACT Long-lasting memories are known to require new transcription. Recent studies have highlighted a role for epigenetic alterations, including histone acetylation, in regulating gene expression. In this issue of Neuron, Alarcón et al. and Korzus et al. use two different mouse models of Rubinstein-Taybi syndrome to elucidate a role for the histone acetyltransferase activity of CREB binding protein (CBP) in long-term memory and plasticity.

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    ABSTRACT: Alzheimer's disease (AD) is the most common type of dementia in the elderly. It is characterized by the deposition of two forms of aggregates within the brain, the amyloid β plaques and tau neurofibrillary tangles. Currently, no disease-modifying agent is approved for the treatment of AD. Approved pharmacotherapies target the peripheral symptoms but they do not prevent or slow down the progression of the disease. Although several disease-modifying immunotherapeutic agents are in clinical development, many have failed due to lack of efficacy or serious adverse events. Epigenetic changes including DNA methylation and histone modifications are involved in learning and memory and have been recently highlighted for holding promise as potential targets for AD therapeutics. Dynamic and latent epigenetic alterations are incorporated in AD pathological pathways and present valuable reversible targets for AD and other neurological disorders. The approval of epigenetic drugs for cancer treatment has opened the door for the development of epigenetic drugs for other disorders including neurodegenerative diseases. In particular, methyl donors and histone deacetylase inhibitors are being investigated for possible therapeutic effects to rescue memory and cognitive decline found in such disorders. This review explores the area of epigenetics for potential AD interventions and presents the most recent findings in this field.
    Pharmacology [?] Therapeutics 04/2013; DOI:10.1016/j.pharmthera.2013.03.010 · 7.75 Impact Factor
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    ABSTRACT: Reporting in a recent issue of Neuron, Yamada et al. (2014) show that the histone deacetylase (HDAC)-containing NuRD complex plays a critical role in shutting down expression of specific synaptogenesis-related genes in the cerebellum, resulting in enhanced differentiation of presynaptic structures. This work suggests that HDACs in neurons acquire specificity through NuRD.
    Developmental Cell 07/2014; 30(1):9-10. DOI:10.1016/j.devcel.2014.06.028 · 10.37 Impact Factor
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    ABSTRACT: PolyADP-ribosylation is a post-translational modification of nuclear proteins, catalyzed by polyADP-ribose polymerases (PARPs). In the nucleus, polyADP-ribosylation catalyzed by PARP-1 alters protein–protein and protein–DNA interactions, and is implicated in chromatin remodeling, DNA transcription, and repair. Previous results linked the activation of PARP-1 with long-term memory formation during learning in the marine mollusk Aplysia ( Science 2004, 304:1820–1822). Furthermore, PARP-1 was highly activated in mammalian cerebral neurons treated with neurotrophins and neurotrophic peptides promoting neurite outgrowth and synaptic plasticity. Here, we examine the possibility that PARP-1 activation is required for memory formation during learning in mammals. Mice were tested in two learning paradigms, object recognition and fear conditioning. PolyADP-ribosylation of PARP-1 and histone H1 were detected in their cerebral cortex and hippocampus immediately after their training session. Moreover, in both behavioral paradigms, suppression of PARP activity in the CNS during learning impaired their long-term memory formation, without damaging their short-term memory. These findings implicate PARP-1 activation in molecular processes underlying long-term memory formation during learning.
    Journal of Neurochemistry 09/2009; 111(1):72 - 79. DOI:10.1111/j.1471-4159.2009.06296.x · 4.24 Impact Factor