Department of Pharmaceutical and Life Sciences, Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba 288-0025, Japan.
Bioorg Med Chem Lett. 2013 Nov 1;23(21):6015-8. doi: 10.1016/j.bmcl.2013.08.001. Epub 2013 Aug 11.
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.
这封信描述了 4-苯丁酸（4-PBA）对内质网（ER）应激诱导的神经元细胞死亡的保护作用的机制，使用了三种简单的 4-（对取代苯基）丁酸（4-PBA 衍生物）。它们对人组蛋白去乙酰化酶（HDAC）的相对抑制活性与它们与 HDAC7 结合的结构模型一致，并且它们能够在体外抑制神经元细胞死亡和化学伴侣的活性。这些数据表明，4-PBA 可以防止化学伴侣活性介导的神经元细胞死亡，而不是通过抑制组蛋白去乙酰化酶。
