Question 1

What is the Meaning of FKBP51?

Accepted Answer

FKBP51, or FK506-binding protein 51, is a co-chaperone protein interacting with the glucocorticoid receptor (GR). It negatively regulates GR signaling, reducing cellular sensitivity to cortisol and other glucocorticoids. It belongs to the immunophilin family.

Question 2

What is the Context of FKBP51?

Accepted Answer

Within cells, FKBP51 resides in cytoplasm and nucleus, participating in stress response. It forms part of a chaperone complex, including Hsp90, essential for regulating folding, trafficking, and activity of steroid hormone receptors, particularly the GR. FKBP51 expression is often induced by glucocorticoids, establishing a negative feedback loop.

Question 3

What is the Significance of FKBP51?

Accepted Answer

FKBP51 holds clinical importance due to its influence on stress hormone regulation and health implications. Altered FKBP51 expression or function can modify glucocorticoid sensitivity, relevant in conditions like major depressive disorder, anxiety disorders, PTSD, and metabolic syndromes. Its role informs strategies for normalizing stress responses.

Question 4

What is the Mechanism of FKBP51?

Accepted Answer

FKBP51 exerts its regulatory effect by directly binding to the glucocorticoid receptor, hindering its nuclear translocation and gene transcription. It achieves this by stabilizing the inactive, ligand-bound GR in the cytoplasm, preventing dissociation from the chaperone complex. This reduces receptor binding affinity, attenuating genomic effects and modulating cellular responses.

Question 5

What is the Application of FKBP51?

Accepted Answer

Clinically, modulating FKBP51 activity or expression represents a therapeutic avenue, particularly in neuropsychiatric disorders linked to dysregulated stress responses. Research explores pharmacological agents to inhibit FKBP51 or modify its interaction with the glucocorticoid receptor to restore balanced stress hormone signaling. Genetic variations are also studied as biomarkers for predicting psychotropic responses.

Question 6

What is the Metric of FKBP51?

Accepted Answer

Assessment of FKBP51 is primarily a research endeavor using molecular biology techniques. Its expression levels can be quantified in biological samples, like tissue biopsies or peripheral blood mononuclear cells, via quantitative PCR or Western blotting. Genetic variations, specifically SNPs within the FKBP51 gene, are analyzed through genotyping to establish correlations with disease susceptibility or therapeutic outcomes. Routine clinical measurement of circulating FKBP51 levels is not standard practice.

Question 7

What is the Risk of FKBP51?

Accepted Answer

Alterations in FKBP51 function, whether from genetic predispositions or interventions, present risks related to glucocorticoid signaling imbalances. Excessive inhibition could lead to heightened cellular sensitivity to glucocorticoids, potentially causing adverse effects from amplified cortisol action, including metabolic dysregulation or immune suppression. Conversely, elevated FKBP51 activity might contribute to glucocorticoid resistance, impeding effective management of inflammatory conditions or increasing vulnerability to stress-related pathologies.

FKBP51

Meaning

Context

Significance

Mechanism

Application

Metric

Risk

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