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• W2045703037 abstract "The interaction between CD40 and its cognate ligand, CD40 ligand, is a primary regulator of the peripheral immune response, including modulation of T lymphocyte activation, B lymphocyte differentiation and antibody secretion, and innate immune cell activation, maturation, and survival. Recently, we and others have identified CD40 expression on a variety of CNS cells, including endothelial cells, smooth muscle cells, astroglia and microglia, and have found that, on many of these cells, CD40 expression is enhanced by pro-inflammatory stimuli. Importantly, the CD40–CD40 ligand interaction on microglia triggers a series of intracellular signaling events that are discussed, beginning with Src-family kinase activation and culminating in microglial activation as evidenced by tumor necrosis factor-α secretion. Based on the involvement of microglial activation and brain inflammation in Alzheimer's disease pathogenesis, we have investigated co-stimulation of microglia, smooth muscle, and endothelial cells with CD40 ligand in the presence of low doses of freshly solubilized amyloid-β peptides. Data reviewed herein show that CD40 ligand and amyloid-β act synergistically to promote pro-inflammatory responses by these cells, including secretion of interleukin-1β by endothelial cells and tumor necrosis factor-α by microglia. As these cytokines have been implicated in neuronal injury, a comprehensive model of pro-inflammatory CD40 ligand and amyloid-β initiated Alzheimer's disease pathogenesis (mediated by multiple CNS cells) is proposed." @default.
• W2045703037 created "2016-06-24" @default.
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• W2045703037 date "2001-11-01" @default.
• W2045703037 modified "2023-10-14" @default.
• W2045703037 title "CD40 signaling and Alzheimer's disease pathogenesis" @default.
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• W2045703037 doi "https://doi.org/10.1016/s0197-0186(01)00044-4" @default.
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• W2045703037 hasPublicationYear "2001" @default.
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