دورية أكاديمية
Activation of TNF Receptor 2 improves synaptic plasticity and enhances amyloid-β clearance in an Alzheimer's disease mouse model with humanized TNF Receptor 2
| العنوان: | Activation of TNF Receptor 2 improves synaptic plasticity and enhances amyloid-β clearance in an Alzheimer's disease mouse model with humanized TNF Receptor 2 |
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| المؤلفون: | Ortí-Casañ, Natalia, Wajant, Harald, Kuiperij, H. Bea, Hooijsma, Annelien, Tromp, Leon, Poortman, Isabelle L., Tadema, Norick, de Lange, Julia H.E., Verbeek, Marcel M., De Deyn, Peter P., Naudé, Petrus J.W., Eisel, Ulrich L.M. |
| المصدر: | Ortí-Casañ , N , Wajant , H , Kuiperij , H B , Hooijsma , A , Tromp , L , Poortman , I L , Tadema , N , de Lange , J H E , Verbeek , M M , De Deyn , P P , Naudé , P J W & Eisel , U L M 2023 , ' Activation of TNF Receptor 2 improves synaptic plasticity and enhances amyloid-β clearance in an Alzheimer's disease mouse model with humanized TNF Receptor 2 ' , Journal of Alzheimer's Disease , vol. 94 , no. 3 , pp. .... |
| سنة النشر: | 2023 |
| المجموعة: | University of Groningen research database |
| مصطلحات موضوعية: | Alzheimer's disease, humanized mouse model, neurodegeneration, neuroinflammation, TNF, TNFR2 agonist |
| الوصف: | Background: Tumor necrosis factor-alpha (TNF-α) is a master cytokine involved in a variety of inflammatory and neurological diseases, including Alzheimer's disease (AD). Therapies that block TNF-α proved ineffective as therapeutic for neurodegenerative diseases, which might be explained by the opposing functions of the two receptors of TNF (TNFRs): while TNFR1 stimulation mediates inflammatory and apoptotic pathways, activation of TNFR2 is related to neuroprotection. Despite the success of targeting TNFR2 in a transgenic AD mouse model, research that better mimics the human context is lacking. Objective: The aim of this study is to investigate whether stimulation of TNFR2 with a TNFR2 agonist is effective in activating human TNFR2 and attenuating AD neuropathology in the J20xhuTNFR2-k/i mouse model. Methods: Transgenic amyloid-β (Aβ)-overexpressing mice containing a human extracellular TNFR2 domain (J20xhuTNFR2-k/i) were treated with a TNFR2 agonist (NewStar2). After treatment, different behavioral tests and immunohistochemical analysis were performed to assess different parameters, such as cognitive functions, plaque deposition, synaptic plasticity, or microglial phagocytosis. Results: Treatment with NewStar2 in J20xhuTNFR2-k/i mice resulted in a drastic decrease in plaque load and beta-secretase 1 (BACE-1) compared to controls. Moreover, TNFR2 stimulation increased microglial phagocytic activity, leading to enhanced Aβ clearance. Finally, activation of TNFR2 rescued cognitive impairments and improved synaptic plasticity. Conclusion: Our findings demonstrate that activation of human TNFR2 ameliorates neuropathology and improves cognitive functions in an AD mouse model. Moreover, our study confirms that the J20xhuTNFR2-k/i mouse model is suitable for testing human TNFR2-specific compounds. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://research.rug.nl/en/publications/ecb7d960-7920-4e16-9a70-323163bd21a7Test |
| DOI: | 10.3233/JAD-221230 |
| الإتاحة: | https://doi.org/10.3233/JAD-221230Test https://hdl.handle.net/11370/ecb7d960-7920-4e16-9a70-323163bd21a7Test https://research.rug.nl/en/publications/ecb7d960-7920-4e16-9a70-323163bd21a7Test https://pure.rug.nl/ws/files/769582694/jad_2023_94-3_jad-94-3-jad221230_jad-94-jad221230_1_.pdfTest http://www.scopus.com/inward/record.url?scp=85166733328&partnerID=8YFLogxKTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.2EFACD27 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3233/JAD-221230 |
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