Vega Hector, Agellon Luis B, Michalak Marek
Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
School of Dietetics and Human Nutrition, McGill University, Quebec, Canada.
IUBMB Life. 2016 Dec;68(12):943-954. doi: 10.1002/iub.1576. Epub 2016 Oct 31.
Molecular chaperones are specialized proteins essential for facilitating the correct folding, assembly, and disassembly of many cellular proteins and for assuring proteostasis. Genetic mutations or metabolic extremes that cause long-term alteration of cellular homeostasis compromise protein folding efficiency. To maintain proteostasis, cells mobilized stress coping responses that include the unfolded protein response in order to prevent accumulation of improperly folded proteins that forms the basis of many diseases. In recent years, several small molecules commonly referred to as "chemical chaperones" (e.g., 4-phenylbutyric acid or 4-PBA, a modified fatty acid; tauroursodeoxycholic acid or TUDCA, a bile acid) have been identified that function to attenuate cellular stress and enhance protein processing. Here we illustrate that molecular chaperones and the so called "chemical chaperones" are distinct entities. We propose the term "proteostasis promoters" as a more accurate descriptor for a class of compounds that demonstrate ability to promote proteostasis by modulating the UPR and/or the function of chaperones. © 2016 IUBMB Life, 68(12):943-954, 2016.
分子伴侣是一类特殊的蛋白质，对于促进许多细胞蛋白质的正确折叠、组装和拆卸以及确保蛋白质稳态至关重要。导致细胞稳态长期改变的基因突变或代谢极端情况会损害蛋白质折叠效率。为了维持蛋白质稳态，细胞会启动应激应对反应，其中包括未折叠蛋白反应，以防止形成许多疾病基础的错误折叠蛋白的积累。近年来，已鉴定出几种通常被称为“化学伴侣”的小分子（例如4-苯基丁酸或4-PBA，一种修饰的脂肪酸；牛磺熊去氧胆酸或TUDCA，一种胆汁酸），它们的作用是减轻细胞应激并增强蛋白质加工。在这里，我们说明分子伴侣和所谓的“化学伴侣”是不同的实体。我们提出“蛋白质稳态促进剂”一词，作为对一类化合物更准确的描述，这类化合物通过调节未折叠蛋白反应和/或伴侣蛋白的功能来证明其促进蛋白质稳态的能力。©2016国际生物化学与分子生物学联盟生命科学部，68(12):943 - 954，2016年。
