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Proinflammatory cytokines TNF- and IL1- activate the canonical NF-B pathway that induce the gene expression of cyclooxigenase-2, inducible nitric oxide synthase-3, inflammatory cytokines, and matrix metalloproteinases [75] These changes lead to the damage of TJs, decreased endothelial integrity and increased permeability at the BBB [73, 76], and to neuroinflammation and the development of chronic neurodegenerative diseases such as AD [10, 77]

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