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• W2069551486 endingPage "968" @default.
• W2069551486 startingPage "959" @default.
• W2069551486 abstract "Objective: Autophagy, the intracellular breakdown system for proteins and some organelles, is considered to be important in neurodegenerative disease. Recent reports suggest that autophagy plays an important role in Alzheimer's disease pathogenesis and autophagic vacuoles (AVs) may be sites of amyloid β protein (Aβ) generation. We attempted to determine if imposed changes in autophagic activity are linked to Aβ generation and secretion in cultured cells. Methods: We used Chinese hamster ovary cells, stably expressing wild-type APP 751. We treated the cells with three known autophagy modulating conditions, rapamycin treatment, U18666A treatment and cholesterol depletion. Results: All the three conditions resulted in increased levels of LC3-II by western blotting, together with an increase in the number of LC3-positive granules. However, the effects on Aβ production were inconsistent. The rapamycin treatment increased Aβ production and secretion, but the other two conditions had opposite effects. When the level of phosphorylation of the mammalian target of rapamycin (mTOR) was measured, down-regulation of phosphorylated mTOR levels was observed only in rapamycin-treated cells. The LC3-positive granules in the U18666A-treated and cholesterol-depleted cells were different from those in rapamycin-treated cells in terms of number, size and distribution, suggesting that degradative process from autophagosomes to lysosomes was disturbed. Discussion: The biochemical pathways leading to autophagy and the generation of AVs appear to be different in cells treated by the three methods. These differences may explain why the similar autophagic status determined by LC3 immunoreactivities does not correlate with Aβ generation and secretion." @default.
• W2069551486 created "2016-06-24" @default.
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• W2069551486 date "2009-11-01" @default.
• W2069551486 modified "2023-10-11" @default.
• W2069551486 title "Variations in the effects on synthesis of amyloid<i>β</i>protein in modulated autophagic conditions" @default.
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• W2069551486 doi "https://doi.org/10.1179/174313209x395463" @default.
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