DOI: 10.1002/ame2.12361
Microglial ApoD-induced NLRC4 inflammasome activation promotes Alzheimer's disease progression
Yaliang Yu1
Jianzhou Lv1
Dan Ma1
Ya Han1
Yaheng Zhang1
Shanlong Wang2
Zhitao Wang1
1.Department of Neurology,The Second Affiliated Hospital of Henan University of Science and Technology,Luoyang,P.R.China2.Clinical Lab,The Second Affiliated Hospital of Henan University of Science and Technology,Luoyang,P.R.China
摘要：Background:Alzheimer's disease(AD)is a progressive neurodegenerative disease with no effective therapies.It is well known that chronic neuroinflammation plays a critical role in the onset and progression of AD.Well-balanced neuronal-microglial interactions are essential for brain functions.However,determining the role of mi-croglia-the primary immune cells in the brain-in neuroinflammation in AD and the associated molecular basis has been challenging.
Methods:Inflammatory factors in the sera of AD patients were detected and their association with microglia activation was analyzed.The mechanism for microglial in-flammation was investigated.IL6 and TNF-α were found to be significantly increased in the AD stage.
Results:Our analysis revealed that microglia were extensively activated in AD cer-ebra,releasing sufficient amounts of cytokines to impair the neural stem cells(NSCs)function.Moreover,the ApoD-induced NLRC4 inflammasome was activated in micro-glia,which gave rise to the proinflammatory phenotype.Targeting the microglial ApoD promoted NSC self-renewal and inhibited neuron apoptosis.These findings demon-strate the critical role of ApoD in microglial inflammasome activation,and for the first time reveal that microglia-induced inflammation suppresses neuronal proliferation.
Conclusion:Our studies establish the cellular basis for microglia activation in AD pro-gression and shed light on cellular interactions important for AD treatment.
机标关键词：alzheimernlrc4activationapod-induceddiseaseinflammasomemicroglialprogression
论文发表日期：2025-03-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：11( 773-783 )
英文信息