The immune system is a complex protective network that is tightly controlled to protect and defend the host.Inflammation is a precisely regulated response that is crucial for host defense,while dysregulation can lead ...The immune system is a complex protective network that is tightly controlled to protect and defend the host.Inflammation is a precisely regulated response that is crucial for host defense,while dysregulation can lead to tissue damage and systemic diseases.Defining the mechanisms that initiate,amplify,and resolve inflammation is crucial for understanding our complex immune system.The inflammasome,a multiprotein complex that functions as a sensor,plays a key role in regulating this inflammatory response.Inflammasomes act as molecular platforms that integrate upstream danger signals,catalyze the activation of caspase-1,and drive the maturation and secretion of proinflammatory cytokines such as IL-1βand IL-18.These inflammatory cytokines are released through pyroptosis,a lytic form of programmed cell death that eliminates infected or damaged cells while simultaneously propagating inflammation through the release of cytokines or chemokines[1].展开更多
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.Wel...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 microglia—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 inflammation 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 cerebra,releasing sufficient amounts of cytokines to impair the neural stem cells(NSCs)function.Moreover,the ApoD-induced NLRC4 inflammasome was activated in microglia,which gave rise to the proinflammatory phenotype.Targeting the microglial ApoD promoted NSC self-renewal and inhibited neuron apoptosis.These findings demonstrate 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 progression and shed light on cellular interactions important for AD treatment.展开更多
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(2022R1C1C1007544,2024M3A9H5043152 to S.L.)a grant from the Korea Drug Development Fund funded by the Ministry of Science and ICT+7 种基金the Ministry of Trade,Industry,and Energythe Ministry of Health and Welfare(RS-2025--02222987 to S.L.)a grant from the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea,under the Korea Health Technology R&D Project(RS-2022--KH128422(HV22C015600)to S.L.)the Institute for Basic Science(IBS),Republic of Korea(IBS-R801--D9-A09,IBS-R801-D1-2025-a02 to S.L.)supported by the Circle Foundation(Republic of Korea)through the selection of the UNIST Pandemic Treatment Research Center as the 2023 Circle Foundation Innovative Science Technology Center(2023 TCF Innovative Science Project-01 to S.L.)Additionally,this study received funding from the Republic of Korea’s National Institute of Health(Project No.#2025ER160200,#2025ER240100 to S.L.)Additional support was provided by research funds from the Ulsan National Institute of Science&Technology(UNIST)(1.220112.01,1.220107.01 to S.L.)a grant from Yuhan Corporation(S.L.).
文摘The immune system is a complex protective network that is tightly controlled to protect and defend the host.Inflammation is a precisely regulated response that is crucial for host defense,while dysregulation can lead to tissue damage and systemic diseases.Defining the mechanisms that initiate,amplify,and resolve inflammation is crucial for understanding our complex immune system.The inflammasome,a multiprotein complex that functions as a sensor,plays a key role in regulating this inflammatory response.Inflammasomes act as molecular platforms that integrate upstream danger signals,catalyze the activation of caspase-1,and drive the maturation and secretion of proinflammatory cytokines such as IL-1βand IL-18.These inflammatory cytokines are released through pyroptosis,a lytic form of programmed cell death that eliminates infected or damaged cells while simultaneously propagating inflammation through the release of cytokines or chemokines[1].
基金supported by the Guiding Science and Technology Development Grant in the Social Sector of Luoyang(2101083A)。
文摘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 microglia—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 inflammation 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 cerebra,releasing sufficient amounts of cytokines to impair the neural stem cells(NSCs)function.Moreover,the ApoD-induced NLRC4 inflammasome was activated in microglia,which gave rise to the proinflammatory phenotype.Targeting the microglial ApoD promoted NSC self-renewal and inhibited neuron apoptosis.These findings demonstrate 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 progression and shed light on cellular interactions important for AD treatment.
