HEBE
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-β and Tau protein depositions, with treatments focusing on single proteins have shown limited success due to the complexity of pathways involved. This study explored the potential of chronokines -protein...
| Autores: | , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:308367 |
| Acceso en línea: | https://ddd.uab.cat/record/308367 https://dx.doi.org/urn:doi:10.1016/j.biopha.2025.117815 |
| Access Level: | acceso abierto |
| Palabra clave: | Alzheimer's disease Chronokine Chimeric protein HEBE Klotho TREM2 TIMP2 Memory impairment |
| Sumario: | Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-β and Tau protein depositions, with treatments focusing on single proteins have shown limited success due to the complexity of pathways involved. This study explored the potential of chronokines -proteins that modulate aging-related processes- as an alternative therapeutic approach. Specifically, we focused on a novel pleiotropic chimeric protein named HEBE, combining s-KL, sTREM2 and TIMP2, guided by bioinformatic analyses to ensure the preservation of each protein's conformation, crucial for their functions. In vitro studies confirmed HEBE's stability and enzymatic activities, even suggesting it has different activities compared to the individual chronokines. In vivo experiments on APP/Tau mice revealed improved learning and memory functions with HEBE treatment, along with decreased levels of phosphorylated Tau and minor effects on amyloid-β levels. These findings suggest that HEBE is as a promising therapeutic candidate for ameliorating memory deficits and reducing pTau in an AD mouse model. |
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