IKKβ deficiency in myeloid cells ameliorates Alzheimer's disease-related symptoms and pathology
| Autor: | Xu Liu, Michael D. Menger, Robert Schomburg, Wenlin Hao, Yang Liu, Klaus Fassbender, Manolis Pasparakis, Livia Fülöp, Yann Decker |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Pathology
medicine.medical_specialty media_common.quotation_subject Inflammation Plaque Amyloid Biology Pathogenesis chemistry.chemical_compound Mice Alzheimer Disease medicine Extracellular Animals Humans Myeloid Cells Internalization Cells Cultured media_common Innate immune system Amyloid beta-Peptides Microglia General Neuroscience Neurodegeneration NF-κB medicine.disease I-kappa B Kinase Mice Inbred C57BL Protein Transport medicine.anatomical_structure chemistry Immunology medicine.symptom Gene Deletion |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 34(39) |
| ISSN: | 1529-2401 |
| Popis: | Alzheimer's disease (AD) is characterized by extracellular amyloid-β (Aβ) deposits and microglia-dominated inflammatory activation. Innate immune signaling controls microglial inflammatory activities and Aβ clearance. However, studies examining innate immunity in Aβ pathology and neuronal degeneration have produced conflicting results. In this study, we investigated the pathogenic role of innate immunity in AD by ablating a key signaling molecule, IKKβ, specifically in the myeloid cells of TgCRND8 APP-transgenic mice. Deficiency of IKKβ in myeloid cells, especially microglia, simultaneously reduced inflammatory activation and Aβ load in the brain and these effects were associated with reduction of cognitive deficits and preservation of synaptic structure proteins. IKKβ deficiency enhanced microglial recruitment to Aβ deposits and facilitated Aβ internalization, perhaps by inhibiting TGF-β-SMAD2/3 signaling, but did not affect Aβ production and efflux. Therefore, inhibition of IKKβ signaling in myeloid cells improves cognitive functions in AD mice by reducing inflammatory activation and enhancing Aβ clearance. These results contribute to a better understanding of AD pathogenesis and could offer a new therapeutic option for delaying AD progression. |
| Databáze: | OpenAIRE |
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