Microglial ApoD-induced NLRC4 inflammasome activation promotes Alzheimer's disease progression.

Autor: Yu Y; Department of Neurology, The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang, P. R. China., Lv J; Department of Neurology, The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang, P. R. China., Ma D; Department of Neurology, The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang, P. R. China., Han Y; Department of Neurology, The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang, P. R. China., Zhang Y; Department of Neurology, The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang, P. R. China., Wang S; Clinical Lab, The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang, P. R. China., Wang Z; Department of Neurology, The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang, P. R. China.
Jazyk: angličtina
Zdroj: Animal models and experimental medicine [Animal Model Exp Med] 2024 Mar 23. Date of Electronic Publication: 2024 Mar 23.
DOI: 10.1002/ame2.12361
Abstrakt: 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.
(© 2023 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)
Databáze: MEDLINE
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