Can 14-3-3 proteins serve as therapeutic targets for the treatment of metabolic diseases?

Since their initial characterization as abundant brain proteins more than 5 decades ago, a resurgence into understanding the cellular functions of 14-3-3 proteins has emerged. While one of the earliest functions attributed to this eukaryotic scaffold protein family was the activation of enzymes involved in catecholamine and serotonin biosynthesis, 14-3-3 proteins have since been implicated in the regulation of several cellular processes including cell-cycle control, apoptosis, and metabolism. Moreover, increasing lines of evidence demonstrate links between changes in 14-3-3 protein function and the pathogenesis of chronic diseases. As a result, this has raised the question of whether 14-3-3 proteins represent viable targets for pharmacological intervention against diseases such as obesity, diabetes and cancer. In addition to providing an overview of the 14-3-3 protein family, we will discuss their connections to metabolism and metabolic diseases. We will also elaborate on the potential of targeting 14-3-3 proteins, as well as components of their interactomes, for developing novel therapies for treating metabolic diseases, including diabetes and obesity.