The FK506 binding protein 51 (FKBP51) has recently been identified as a promising therapeutic target for stress-related psychiatric disorders and obesity-related metabolic outcomes.
Genetic and epigenetic alterations in FK506-binding protein 5 ( FKBP5) have been associated with increased risk for psychiatric disorders, including post-traumatic stress disorder (PTSD).
FKBP5 presents the possibility to better understand the molecular and cellular factors contributing to a disease-relevant gene by environment interaction, with implications for the development of biomarkers and interventions for psychiatric disorders.
Given the association of these maladaptive emotion regulation processes and psychiatric disorders, the findings suggest possible psychological mechanisms why FKBP5 haplotype carriers exposed to childhood trauma are more vulnerable to developing a psychiatric disorder later in life.
FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity.
Here, we report that exposing mice to chronic stress led to a specific increase in microRNA-15a levels in the amygdala-Ago2 complex and a concomitant reduction in the levels of its predicted target, FKBP51, which is implicated in stress-related psychiatric disorders.
We present recent evidence related to epigenetic regulation of genes involved in hypothalamus-pituitary-adrenal axis regulation, namely, the glucocorticoid receptor gene (nuclear receptor subfamily 3, group C, member 1 [NR3C1]) and FK506 binding protein 51 gene (FKBP5), after childhood adversity and associations with risk for psychiatric disorders.
Single nucleotide polymorphisms (SNPs) in the FKBP5 gene have been shown to interact with retrospectively self-reported early life stress (ELS) in patients with psychiatric disorders.
The FK506-binding protein 51 (FKBP51, encoded by the FKBP5 gene) is an established risk factor for stress-related psychiatric disorders such as major depression.
The common single nucleotide polymorphism (SNP) rs1360780 (C/T) of the FK506 Binding Protein 5 (FKBP5) gene has been reported to be associated with an altered response of the hypothalamic-pituitary-adrenal (HPA) axis and the development of stress-related psychiatric disorders such as posttraumatic stress disorder (PTSD).
The study of intermediate phenotypes, such as emotion-processing biases and their neural substrates, provides a way to clarify the mechanisms by which FKBP5 dysregulation mediates risk for psychiatric disorders.
We found that a functional polymorphism altering chromatin interaction between the transcription start site and long-range enhancers in the FK506 binding protein 5 (FKBP5) gene, an important regulator of the stress hormone system, increased the risk of developing stress-related psychiatric disorders in adulthood by allele-specific, childhood trauma-dependent DNA demethylation in functional glucocorticoid response elements of FKBP5.
As a result, FKBP51 now lies at the heart of the research of many stress related psychiatric disorders, which has led to advances in the understanding of this protein and its role in humans and in animal models.