The rise of proteostasis promoters.

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.