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Schlagwörter:
FKBP5, FKBP51
Zusammenfassung:
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 cochaperone 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.
