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Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702
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Abstract

Introduction

Our previous work has demonstrated significant effects on the oxidative stress response, mitochondrial function, and oxidative phosphorylation in the livers and intestines of p300 S89A knockin (S89AKI) mice. We now show that this mutation is also associated with brain metabolic defects and neuronal differentiation.

Methods

p300 S89A edited P19 cells, and S89AKI mice demonstrated metabolic and neuronal differentiation defects based on proteomic, cell biological and PET imaging studies.

Results

The metabolic and differentiation defects associated with the p300 S89A knockin mutation could be corrected both and utilizing the small molecule CBP/beta-catenin antagonist ICG-001.

Conclusion

Rebalancing the equilibrium between CBP/β-catenin p300/β-catenin associated transcription, utilizing the small molecule CBP/beta-catenin antagonist ICG-001, enhances mitochondrial oxidative phosphorylation, metabolic function, and neuronal differentiation and may be able to ameliorate the cognitive decline seen in neurodegenerative disorders, including Alzheimer’s Disease.

© 2024 The Author(s). Published by Bentham Science Publisher.
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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2023-08-28
2024-11-23

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Differential Kat3 Coactivator Usage Regulates Brain Metabolism and Neuronal Differentiation
Curr Mol Pharmacol 17, e170823219875 (2024); https://doi.org/10.2174/1874467217666230817092415
/content/journals/cmp/10.2174/1874467217666230817092415
/content/journals/cmp/10.2174/1874467217666230817092415
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  • Article Type:     Research Article
Keyword(s): CBP; ICG-001; Kat3; Metabolism; Neurodegeneration; p300

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