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| Home > In process > Effects of FKBP5 on Stroke Outcome in Mice and Men-a Translational Study. |
| Home > In process > Effects of FKBP5 on Stroke Outcome in Mice and Men-a Translational Study. |
| Journal Article | DZNE-2026-00406 |
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2026
Association
New York, NY
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Please use a persistent id in citations: doi:10.1161/STROKEAHA.125.052905
Abstract: FKBP5 (FK506-binding protein 51, protein), encoded by the FKBP5 (gene, human), is a glucocorticoid receptor-regulating cochaperone. FKBP5 has been suggested as a mediator between stress, vascular morbidity, and neuropsychiatric complications. In this translational proof-of-concept study, we investigated the impact of FKBP5 on stroke outcome in mice and men.Fkbp5 (gene, mouse) knockout and wild-type mice were subjected to transient brain ischemia. Lesion volume was assessed at 48 hours after stroke using magnetic resonance imaging. Circulating corticosterone level and adrenal gland weight were determined at 72 hours. Observational data from the Prospective Cohort with Incident Stroke Berlin were used to explore associations between FKBP5 gene variants and functional outcome after 1 year. Poor functional outcome at 1 year was defined as a modified Rankin Scale score of 0 to 1 versus 2 to 6. Risk allele ACT from a predefined FKBP5 haplotype (rs9296158, rs3800373, rs1360780) versus non-ACT was used as the exposure variable. Logistic regression analyses were performed and adjusted for potential confounders.Fkbp5 knockout mice showed reduced corticosterone levels and adrenal weights, together with smaller infarct lesions at 48 hours. Four hundred thirty-three patients with available FKBP5 haplotype were included in the Berlin stroke cohort. FKBP5 risk haplotype ACT, which was present in 204 patients, was associated with poor functional outcome at 1 year (adjusted odds ratio, 1.7 [95% CI, 1.02-2.7]).Loss of Fkbp5 leads to improved outcome in experimental stroke. In addition, the FKBP5 risk haplotype, indicative of increased FKBP5 expression, was associated with poor functional outcome following stroke.
Keyword(s): adrenal gland ; alleles ; corticosterone ; haplotype ; morbidity
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