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

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作  者:Sophie Steeland Roosmarijn E.Vandenbroucke 

机构地区:[1]VIB Center for Inflammation Research,Ghent,Belgium [2]Department of Biomedical Molecular Biology,Ghent University,Ghent,Belgium

出  处:《中国神经再生研究:英文版》2019年第7期1144-1147,共4页Neural Regeneration Research

基  金: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).

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 medicine.Novel insights highlight the importance of neuroinflammation as an undeniable player in the onset and progression of Alzheimer’s disease.Tumor 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 disease.However,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 trials.We 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 1.In agreement with this,choroidal tumor necrosis factor/tumor necrosis factor receptor 1 signaling was also upregulated in different Alzheimer’s disease mouse models.Interestingly,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 functioning.Here,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 progression.As 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 of Alzheimer’s disease and pr

关 键 词:tumor necrosis factor NEUROINFLAMMATION blood-cerebrospinal fluid barrier PRECLINICAL research drug development NEURODEGENERATION cognitive decline mouse models TNFR 

分 类 号:R749.16[医药卫生—神经病学与精神病学;医药卫生—临床医学]

 

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