Choroid plexus tumor necrosis factor receptor 1:a new neuroinflammatory piece of the complex Alzheimer's disease puzzle

作     者：Sophie Steeland Roosmarijn E.Vandenbroucke 

作者机构：VIB Center for Inflammation Research Department of Biomedical Molecular BiologyGhent University 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2019年第14卷第7期

页      面：1144-1147页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100203[医学-老年医学] 10[医学] 

基　　金：supported by the Research Foundation Flanders(FWO) The Foundation for Alzheimer’s Research Belgium(SAO-FRA) European Union Cost action MouseAge(BM1402) the Baillet Latour Fund(all to SS and REV) 

主　　题：tumor necrosis factor neuroinflammation blood-cerebrospinal fluid barrier preclinical research drug development neurodegeneration cognitive decline mouse models TNFR 

摘      要：Due to the aging of the population and despite the enormous scientific effort,Alzheimer s disease remains one of the biggest medical and pharmaceutical challenges in current *** insights highlight the importance of neuroinflammation as an undeniable player in the onset and progression of Alzheimer s *** necrosis factor is a master inflammatory cytokine that signals via tumor necrosis factor receptor 1 and tumor necrosis factor receptor 2,but that also regulates several brain functions in health and ***,clinical trials investigating drugs that interfere with the tumor necrosis factor pathway in Alzheimer s disease led to inconclusive results,partially because not only the pro-inflammatory tumor necrosis factor/tumor necrosis factor receptor 1,but also the beneficial tumor necrosis factor/tumor necrosis factor receptor 2 signaling was antagonized in these *** recently found that tumor necrosis factor is the main upregulated cytokine in the choroid plexus of Alzheimer s disease patients,signaling via tumor necrosis factor receptor *** agreement with this,choroidal tumor necrosis factor/tumor necrosis factor receptor 1 signaling was also upregulated in different Alzheimer s disease mouse ***,both genetic and nanobody-based pharmacological blockage of tumor necrosis factor receptor 1 signaling was accompanied by favorable effects on Alzheimer s disease-associated inflammation,choroidal morphology and cognitive ***,we briefly summarize the detrimental effects that can be mediated by tumor necrosis factor/tumor necrosis factor receptor 1 signaling in(early) Alzheimer s disease,and the consequences this might have on the disease *** the main hypothesis in Alzheimer s disease clinical trials is still based on the amyloid beta-cascade,the importance of Alzheimer s disease-associated neuroinflammation urge the development of novel therapeutic strategies that might be effective in the early stages