4-Phenylbutyric acid protects against neuronal cell death by primarily acting as a chemical chaperone rather than histone deacetylase inhibitor

S Mimori, H Ohtaka, Y Koshikawa, K Kawada… - Bioorganic & medicinal …, 2013 - Elsevier
S Mimori, H Ohtaka, Y Koshikawa, K Kawada, M Kaneko, Y Okuma, Y Nomura, Y Murakami…
Bioorganic & medicinal chemistry letters, 2013Elsevier
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 …
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.
Elsevier