ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
A novel activator of CBP/p300 acetyltransferases promotes neurogenesis and extends memory duration in adult mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 164 citations in OpenAlex.
- p300-mediated histone H3K18 lactylation promotes mitochondrial ROS accumulation via mitophagy inhibition to potentiate dopamine agonists efficacy in prolactinomas.Redox biology · 2026Article
- Aerobic exercise facilitates p300 nuclear translocation via ADRB2-AMPKα signaling, leading to enhanced histone acetylation and mitigation of cognitive decline in APP/PS1 mice.Alzheimer's research & therapy · 2026Article
- Histone and non-histone (de)acetylation impact on the blood-brain barrier.Fluids and barriers of the CNS · 2026Review
- Epigenetic Regulation in Ischemic Neuroprotection: The Dual Role of HDACs and HATs in Neuroinflammation and Recovery.Antioxidants (Basel, Switzerland) · 2025Review
- Review
- Epigenetic modulation rescues neurodevelopmental deficits in Syngap1Aging cell · 2025Article
- Potential therapeutic targets for ischemic stroke in pre-clinical studies: Epigenetic-modifying enzymes DNMT/TET and HAT/HDAC.Frontiers in pharmacology · 2025Review
- Epigenetics Modulators as Therapeutics for Neurological Disorders.Current pharmaceutical design · 2025Review
- Eosinophils in Rheumatoid Arthritis: A Multifaceted Role in the Pathogenesis of the Disease.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2025Article
- The Lysine Acetyltransferase PCAF Functionally Interacts with Estrogen Receptor Alpha in the Hippocampus of Gonadally Intact Male-But Not Female-Rats to Enhance Short-Term Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Alzheimer's Disease-Related Epigenetic Changes: Novel Therapeutic Targets.Molecular neurobiology · 2024Review
- Histone acetylation in an Alzheimer's disease cell model promotes homeostatic amyloid-reducing pathways.Acta neuropathologica communications · 2024Article
- DNA methylation, histone acetylation in the regulation of memory and its modulation during aging.Frontiers in aging · 2024Review
- Histone H3 Acetylation Is Involved in Retinoid Acid-Induced Neural Differentiation through Increasing Mitochondrial Function.Biomedicines · 2023Article
- The evolution of small molecule enzyme activators.RSC medicinal chemistry · 2023Review
- The Role of CREBBP/EP300 and Its Therapeutic Implications in Hematological Malignancies.Cancers · 2023Review
- Small molecule modulators of chromatin remodeling: from neurodevelopment to neurodegeneration.Cell & bioscience · 2023Review
- Molecular and functional characterization of an evolutionarily conserved CREB-binding protein in the Lymnaea CNS.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Extracellular matrix stiffness controls cardiac valve myofibroblast activation through epigenetic remodeling.Bioengineering & translational medicine · 2022Article
- CBP/p300 activation promotes axon growth, sprouting, and synaptic plasticity in chronic experimental spinal cord injury with severe disability.PLoS biology · 2022Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the brain functions of specific acetyltransferases such as the CREB-binding protein (CBP) and p300 have been well documented using mutant transgenic mice models, studies based on their direct pharmacological activation are still missing due to the lack of cell-permeable activators. Here we present a small-molecule (TTK21) activator of the histone acetyltransferases CBP/p300, which, when conjugated to glucose-based carbon nanosphere (CSP), passed the blood-brain barrier, induced no toxicity, and reached different parts of the brain. After intraperitoneal administration in mice, CSP-TTK21 significantly acetylated histones in the hippocampus and frontal cortex. Remarkably, CSP-TTK21 treatment promoted the formation of long and highly branched doublecortin-positive neurons in the subgranular zone of the dentate gyrus and reduced BrdU incorporation, suggesting that CBP/p300 activation favors maturation and differentiation of adult neuronal progenitors. In addition, mRNA levels of the neuroD1 differentiation marker and BDNF, a neurotrophin required for the terminal differentiation of newly generated neurons, were both increased in the hippocampus concomitantly with an enrichment of acetylated-histone on their proximal promoter. Finally, we found that CBP/p300 activation during a spatial training, while not improving retention of a recent memory, resulted in a significant extension of memory duration. This report is the first evidence for CBP/p300-mediated histone acetylation in the brain by an activator molecule, which has beneficial implications for the brain functions of adult neurogenesis and long-term memory. We propose that direct stimulation of acetyltransferase function could be useful in terms of therapeutic options for brain diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.