Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 23, Issue 21, Pages 6015-6018Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2013.08.001
Keywords
4-phenylbutyric acid (4-PBA); Chemical chaperone; Histone deacetylase (HDAC); Acetyl histone H3; Endoplasmic reticulum (ER) stress
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Funding
- Japan Science Society
- Ministry of Education, Culture, Sports, Science and Technology, Japan [21590101, 21300142, 20659013, 21590120, 24590119, 24790085]
- Grants-in-Aid for Scientific Research [24590119, 24790085, 23790095, 21300142, 21590101, 20659013, 21590120] Funding Source: KAKEN
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This letter describes the mechanism behind the protective effect of 4-phenylbutyric acid (4-PBA) against endoplasmic reticulum (ER) stress-induced neuronal cell death using three simple 4-(p-substituted phenyl) butyric acids (4-PBA derivatives). Their relative human histone deacetylase (HDAC) inhibitory activities were consistent with a structural model of their binding to HDAC7, and their ability to suppress neuronal cell death and activity of chemical chaperone in vitro. These data suggest that 4-PBA protects against neuronal cell death mediated by the chemical chaperone activity rather than by inhibition of histone deacetylase. (C) 2013 Elsevier Ltd. All rights reserved.
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