The Role of the Glucocorticoid Receptor and Its Phosphorylation in Neurological Disorders

Hormone-dependent phosphorylation of steroid receptors is a mechanism for modulating glucocorticoid receptor (GR) transcriptional responses. Evidence indicates that GR phosphorylation can influence receptor transcriptional activation in a gene-specific manner, which could have positive or negative impacts, where the relative level of phosphorylation is an important determinant of overall GR function. This review provides insights into the regulatory mechanism of GR phosphorylation in the brain, cellular and molecular specificity affecting neurovascular function, and the impact of GR phosphorylation in neurological disorders. Furthermore, the role of various endogenous and exogenous factors and sex-dependent associations with GR functional changes due to phosphorylation and other interlinking mechanisms are considered. Finally, we highlight the potential therapeutic approaches which have been evaluated, while challenging GR phosphorylation and the overall influence on the activity of GR in brain disorders.