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: 15.05).
07/2004; 42(6):879-81. DOI: 10.1016/j.neuron.2004.06.007
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.
Available from: Nasser Zawia
- "MeCP2 levels are found to decrease with age in primates (Bihaqi et al., 2011). Histone acetylation is also involved in the regulation of learning and memory (Levenson et al., 2004; Martin & Sun, 2004). The most widely studied histone modification is regulated by two groups of enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). "
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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; 139(1). DOI:10.1016/j.pharmthera.2013.03.010 · 9.72 Impact Factor
Available from: Illana Gozes
- "Journal Compilation Ó 2009 International Society for Neurochemistry, J. Neurochem. (2009) 111, 72–79 Ó 2009 The Authors 2003; Li et al. 2003; Purcell et al. 2003; Buchwalter et al. 2004; Korzus et al. 2004; Martin and Sun 2004; Sng et al. 2004; Fischer et al. 2007; Thomson et al. 1999; Guzowski et al. 2001 "
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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 · 4.28 Impact Factor
Available from: Hitoshi Okazawa
- "Therefore, PQBP-1 seems to be involved in brain development, neuronal function and neurodegeneration. Interestingly, CREB-binding protein seems to play similar pathophysiological roles because it is involved in the pathology of polyglutamine diseases (Kazantsev et al. 1999; McCampbell et al. 2000; Steffan et al. 2000; Nucifora et al. 2001) and its mutations cause human mental retardation (see review by Martin and Sun 2004). "
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ABSTRACT: Polyglutamine tract-binding protein-1 (PQBP-1) is a nuclear protein that interacts and colocalizes with mutant polyglutamine proteins. We previously reported that PQBP-1 transgenic mice show a late-onset motor neuron disease-like phenotype and cell death of motor neurons analogous to human neurodegeneration. To investigate the molecular mechanisms underlying the motor neuron death, we performed microarray analyses using the anterior horn tissues of the spinal cord and compared gene expression profiles between pre-symptomatic transgenic and age-matched control mice. Surprisingly, half of the spots changed more than 1.5-fold turned out to be genes transcribed from the mitochondrial genome. Northern and western analyses confirmed up-regulation of representative mitochondrial genes, cytochrome c oxidase (COX) subunit 1 and 2. Immunohistochemistry revealed that COX1 and COX2 proteins are increased in spinal motor neurons. Electron microscopic analyses revealed morphological abnormalities of mitochondria in the motor neurons. PQBP-1 overexpression in primary neurons by adenovirus vector induced abnormalities of mitochondrial membrane potential from day 5, while cytochrome c release and caspase 3 activation were observed on day 9. An increase of cell death by PQBP-1 was also confirmed on day 9. Collectively, these results indicate that dysfunction of PQBP-1 induces mitochondrial stress, a key molecular pathomechanism that is shared among human neurodegenerative disorders.
Journal of Neurochemistry 12/2005; 95(3):858-70. DOI:10.1111/j.1471-4159.2005.03405.x · 4.28 Impact Factor
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