Gene-Stress-Epigenetic Regulation of FKBP5: Clinical and Translational Implications.


Journal Article (Review)

Stress responses and related outcomes vary markedly across individuals. Elucidating the molecular underpinnings of this variability is of great relevance for developing individualized prevention strategies and treatments for stress-related disorders. An important modulator of stress responses is the FK506-binding protein 51 (FKBP5/FKBP51). FKBP5 acts as a co-chaperone that modulates not only glucocorticoid receptor activity in response to stressors but also a multitude of other cellular processes in both the brain and periphery. Notably, the FKBP5 gene is regulated via complex interactions among environmental stressors, FKBP5 genetic variants, and epigenetic modifications of glucocorticoid-responsive genomic sites. These interactions can result in FKBP5 disinhibition that has been shown to contribute to a number of aberrant phenotypes in both rodents and humans. Consequently, FKBP5 blockade may hold promise as treatment intervention for stress-related disorders, and recently developed selective FKBP5 blockers show encouraging results in vitro and in rodent models. Although risk for stress-related disorders is conferred by multiple environmental and genetic factors, the findings related to FKBP5 illustrate how a deeper understanding of the molecular and systemic mechanisms underlying specific gene-environment interactions may provide insights into the pathogenesis of stress-related disorders.

Full Text

Duke Authors

Cited Authors

  • Zannas, AS; Wiechmann, T; Gassen, NC; Binder, EB

Published Date

  • January 2016

Published In

Volume / Issue

  • 41 / 1

Start / End Page

  • 261 - 274

PubMed ID

  • 26250598

Pubmed Central ID

  • 26250598

Electronic International Standard Serial Number (EISSN)

  • 1740-634X

Digital Object Identifier (DOI)

  • 10.1038/npp.2015.235


  • eng

Conference Location

  • England