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- W2023646960 abstract "Amyloid beta (A beta) peptides are produced by sequential cleavages of the Amyloid Precursor Protein (APP) by beta-secretase, Beta-site APP Cleaving Enzyme 1 (BACE1), and by the high molecular weight protein complex gamma-secretase. Central to the amyloid hypothesis, A beta peptides harbor a neurotoxicity that could contribute to the degeneration in Alzheimer's Disease (AD). Thus, therapeutic strategies directed against amyloid beta processing are appealing. Oxidative stress and inflammation stigmata are detectable in AD brains. Together with amyloid peptides, these stresses are known to activate the transcription factor nuclear factor-kappa B (NF-kappa B). We previously showed that NF-kappa B mediated A beta-dependent regulation of BACE1 transcriptional activity (Buggia-Prevot et al., 2008, JBC 283). The objective of the study is to further delineate the putative control of APP, BACE1 and gamma-secretase complex proteins by NF-kappa B. Human Embryonic Kidney cells stably transfected with Swedish APP (sweAPP) or control Mock were transiently transfected with activating or inhibitory kinases of NF-kappa B pathway. The transcriptional activity and protein levels of APP, BACE1 and gamma-secretase protein members were determined, as well as the beta- and gamma-secretases activities, and amyloid beta secretion. The activation of NF-kappa B results in reduced A beta secretion in HEK Mock cells, while it was increased in HEK sweAPP. Transcriptional activities and protein levels of APP, BACE1 and gamma-secretase proteins, as well as enzymatic activities were modulated by NF-kappa B. Our study suggests that, in physiological conditions, NF-kappa B behaves as an inhibitor of amyloid beta production. Conversely, in experimental conditions where supraphysiological concentrations of amyloid beta are reached, NF-kappa B activation contributes to exacerbate A beta production." @default.
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- W2023646960 date "2011-07-01" @default.
- W2023646960 modified "2023-10-17" @default.
- W2023646960 title "P2-223: Regulation of the amyloid precursor protein processing by the Nuclear Factor-kappa B" @default.
- W2023646960 doi "https://doi.org/10.1016/j.jalz.2011.05.1105" @default.
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