Counteracting the effects of TNF receptor-1 has therapeutic potential in Alzheimer's disease.
2018
Аутори:
Steeland, SophieGorlé, Nina
Vandendriessche, Charysse
Balusu, Sriram
Brkić, Marjana
Van Cauwenberghe, Caroline
Van Imschoot, Griet
Van Wonterghem, Elien
De Rycke, Riet
Kremer, Anneke
Lippens, Saskia
Stopa, Edward
Johanson, Conrad E
Libert, Claude
Vandenbroucke, Roosmarijn E
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
Alzheimer's disease (AD) is the most common form of dementia, and neuroinflammation is an important hallmark of the pathogenesis. Tumor necrosis factor (TNF) might be detrimental in AD, though the results coming from clinical trials on anti-TNF inhibitors are inconclusive. TNFR1, one of the TNF signaling receptors, contributes to the pathogenesis of AD by mediating neuronal cell death. The blood-cerebrospinal fluid (CSF) barrier consists of a monolayer of choroid plexus epithelial (CPE) cells, and AD is associated with changes in CPE cell morphology. Here, we report that TNF is the main inflammatory upstream mediator in choroid plexus tissue in AD patients. This was confirmed in two murine AD models: transgenic APP/PS1 mice and intracerebroventricular (icv) AβO injection. TNFR1 contributes to the morphological damage of CPE cells in AD, and TNFR1 abrogation reduces brain inflammation and prevents blood-CSF barrier impairment. In APP/PS1 transgenic mice, TNFR1 deficiency ameliorated amyloidosis. Ultimately, genetic and pharmacological blockage of TNFR1 rescued from the induced cognitive impairments. Our data indicate that TNFR1 is a promising therapeutic target for AD treatment.
Кључне речи:
Alzheimer's disease; TNF receptor 1; Blood‐CSF barrier; Choroid plexus; TherapyИзвор:
EMBO Molecular Medicine, 2018Финансирање / пројекти:
- Fonds Wetenschappelijk Onderzoek (FWO)
- Foundation for Alzheimer's Research (SAO/FRA) Belgium
- European Cooperation in Science and Technology (COST) BM1402
- Ghent University
- Baillet Latour Fund
DOI: 10.15252/emmm.201708300
ISSN: 1757-4676
PubMed: 29472246