Academic Journal
Effects of FKBP5 on Stroke Outcome in Mice and Men—a Translational Study
| Τίτλος: | Effects of FKBP5 on Stroke Outcome in Mice and Men—a Translational Study |
|---|---|
| Συγγραφείς: | Liman, Thomas G., Herzog, Marie-Louise, Czamara, Darina, Göttert, Ria, Schmidt, Mathias V., Kronenberg, Golo, Binder, Elisabeth B., Gertz, Karen, Endres, Matthias |
| Πηγή: | Stroke ; ISSN 0039-2499 1524-4628 |
| Στοιχεία εκδότη: | Ovid Technologies (Wolters Kluwer Health) |
| Έτος έκδοσης: | 2026 |
| Περιγραφή: | BACKGROUND: 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. METHODS: 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. RESULTS: 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]). CONCLUSIONS: Loss of Fkbp 5 leads to improved outcome in experimental stroke. In addition, the FKBP 5 risk haplotype, indicative of increased FKBP5 expression, was associated with poor functional outcome following stroke. |
| Τύπος εγγράφου: | article in journal/newspaper |
| Γλώσσα: | English |
| DOI: | 10.1161/strokeaha.125.052905 |
| DOI: | 10.1161/STROKEAHA.125.052905 |
| Διαθεσιμότητα: | https://doi.org/10.1161/strokeaha.125.052905 https://www.ahajournals.org/doi/full/10.1161/STROKEAHA.125.052905 |
| Αριθμός Καταχώρησης: | edsbas.D077733F |
| Βάση Δεδομένων: | BASE |
| FullText | Text: Availability: 0 CustomLinks: – Url: https://doi.org/10.1161/strokeaha.125.052905# Name: EDS - BASE (ns324271) Category: fullText Text: View record from BASE |
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| Items | – Name: Title Label: Title Group: Ti Data: Effects of FKBP5 on Stroke Outcome in Mice and Men—a Translational Study – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Liman%2C+Thomas+G%2E%22">Liman, Thomas G.</searchLink><br /><searchLink fieldCode="AR" term="%22Herzog%2C+Marie-Louise%22">Herzog, Marie-Louise</searchLink><br /><searchLink fieldCode="AR" term="%22Czamara%2C+Darina%22">Czamara, Darina</searchLink><br /><searchLink fieldCode="AR" term="%22Göttert%2C+Ria%22">Göttert, Ria</searchLink><br /><searchLink fieldCode="AR" term="%22Schmidt%2C+Mathias+V%2E%22">Schmidt, Mathias V.</searchLink><br /><searchLink fieldCode="AR" term="%22Kronenberg%2C+Golo%22">Kronenberg, Golo</searchLink><br /><searchLink fieldCode="AR" term="%22Binder%2C+Elisabeth+B%2E%22">Binder, Elisabeth B.</searchLink><br /><searchLink fieldCode="AR" term="%22Gertz%2C+Karen%22">Gertz, Karen</searchLink><br /><searchLink fieldCode="AR" term="%22Endres%2C+Matthias%22">Endres, Matthias</searchLink> – Name: TitleSource Label: Source Group: Src Data: Stroke ; ISSN 0039-2499 1524-4628 – Name: Publisher Label: Publisher Information Group: PubInfo Data: Ovid Technologies (Wolters Kluwer Health) – Name: DatePubCY Label: Publication Year Group: Date Data: 2026 – Name: Abstract Label: Description Group: Ab Data: BACKGROUND: 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. METHODS: 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. RESULTS: 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]). CONCLUSIONS: Loss of Fkbp 5 leads to improved outcome in experimental stroke. In addition, the FKBP 5 risk haplotype, indicative of increased FKBP5 expression, was associated with poor functional outcome following stroke. – Name: TypeDocument Label: Document Type Group: TypDoc Data: article in journal/newspaper – Name: Language Label: Language Group: Lang Data: English – Name: DOI Label: DOI Group: ID Data: 10.1161/strokeaha.125.052905 – Name: DOI Label: DOI Group: ID Data: 10.1161/STROKEAHA.125.052905 – Name: URL Label: Availability Group: URL Data: https://doi.org/10.1161/strokeaha.125.052905<br />https://www.ahajournals.org/doi/full/10.1161/STROKEAHA.125.052905 – Name: AN Label: Accession Number Group: ID Data: edsbas.D077733F |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1161/strokeaha.125.052905 Languages: – Text: English Titles: – TitleFull: Effects of FKBP5 on Stroke Outcome in Mice and Men—a Translational Study Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Liman, Thomas G. – PersonEntity: Name: NameFull: Herzog, Marie-Louise – PersonEntity: Name: NameFull: Czamara, Darina – PersonEntity: Name: NameFull: Göttert, Ria – PersonEntity: Name: NameFull: Schmidt, Mathias V. – PersonEntity: Name: NameFull: Kronenberg, Golo – PersonEntity: Name: NameFull: Binder, Elisabeth B. – PersonEntity: Name: NameFull: Gertz, Karen – PersonEntity: Name: NameFull: Endres, Matthias IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 01 Type: published Y: 2026 Identifiers: – Type: issn-locals Value: edsbas Titles: – TitleFull: Stroke ; ISSN 0039-2499 1524-4628 Type: main |
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