The FK506-binding protein 51 (FKBP51) has emerged as a key regulator of endocrine stress responses in mammals and as a potential therapeutic target for stress-related disorders (depression, post-traumatic stress disorder), metabolic disorders (obesity and diabetes) and chronic pain.
In the model of depression employed here, decreases in MR expression and GR co-chaperone (FKBP51) levels in the hippocampus were also observed, and HFD intensified the prenatal stress-induced changes in MR expression.
Depression has been linked to dysfunction of the intracellular response system to corticosteroids at the level of the hippocampus (HC) and prefrontal cortex (PFC) with a notable role of the glucocorticoid receptor (GR) and its co-chaperones (FKBP5 and FKBP4).
Importantly, the clinical antidepressant response of patients with depression (n = 51) could be predicted by the antidepressant response of autophagic markers in patient-derived peripheral blood lymphocytes cultivated and treated ex vivo (Beclin1/amitriptyline: r = 0.572, p = 0.003; Beclin1/PAR: r = 0.569, p = 0.004; Beclin1/fluoxetine: r = 0.454, p = 0.026; pAkt/amitriptyline: r = -0.416, p = 0.006; pAkt/PAR: r = -0.355, p = 0.021; LC3B-II/PAR: r = 0.453, p = 0.02), as well as by the lymphocytic expression levels of FKBP51 (r = 0.631, p<0.0001), pAkt (r = -0.515, p = 0.003), and Beclin1 (r = 0.521, p = 0.002) at admission.
More recently, several research groups have consistently shown a protective effect of FKBP51 knockout or knockdown on stress endocrinology and stress-coping behavior in animal models of depression and anxiety.
Genetic variations of the FK506-binding protein of 51-kDa, FKBP51, one of the immunophilins bound to those steroid receptor complexes, were associated with the effectiveness of treatments against depression and with a major risk-factor for the development of post-traumatic stress disorders.