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4-Phenylbutyric acid protects against neuronal cell death by primarily acting as a chemical chaperone rather than histone deacetylase inhibitor |
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| Authors: | Seisuke Mimori Hiroyasu Ohtaka Yukari Koshikawa Koichi Kawada Masayuki Kaneko Yasunobu Okuma Yasuyuki Nomura Yasuoki Murakami Hiroshi Hamana |
| Affiliation: | 1. Department of Pharmaceutical and Life Sciences, Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba 288-0025, Japan;2. Department of Pharmacy, Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba 288-0025, Japan;3. Laboratory of Pharmacotherapeutics, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu, Gifu 501-1196, Japan;4. Department of Pharmacology, Kurume University School of Medicine, 67 Asahimachi, Kurume 830-0011, Japan |
| Abstract: | 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. |
| Keywords: | 4-phenylbutyric acid (4-PBA) Chemical chaperone Histone deacetylase (HDAC) Acetyl histone H3 Endoplasmic reticulum (ER) stress |
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