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• W2899200114 abstract "Amyloid accumulation in the brain is the major pathological hallmark of Alzheimer disease (AD). Amyloid beta (Aβ) is cleared by the endosomal‐autophagy‐lysosomal system, which is impaired in AD pathogenesis by an unknown mechanism. Pseudoginsenoside‐F11 (PF11), an ocotillol‐type ginsenoside, has been demonstrated to decrease the level of Aβ in APP/PS1 mouse brain and to protect neurons by inhibiting the activation of microglia in vitro. The present study showed that PF11 was capable of increasing the uptake and degradation of oligomeric Aβ in cultured microglia. Oligomeric Aβ (oAβ) interrupted the autophagy‐lysosomal degradative system by regulating the nuclear translocation of transcription factor EB (TFEB), a master factor in lysosomal biogenesis. Conversion of Rab5 to Rab7, which is important for the mechanism of cargo progression from early to late endosomes, was also interrupted by high‐concentration oAβ. Notably, in the PF11‐treated microglial cells, a dramatic increase of the lysosome‐associated proteins and enzyme expression were observed, along with the intracellular pH steady state, indicating the improvement of lysosomal function. In addition, PF11 induced TFEB nuclear translocation in microglia treated with high‐concentration oAβ. Furthermore, PF11 was able to restore Rab conversion, suggesting an effective role of PF11 in the maturation of endosomes. These data provide evidence that PF11 can reverse the dysfunction of the endosomal‐lysosomal system induced by high‐concentration oAβ in microglia, and this might be the main mechanism by which PF11 facilitates oAβ clearance. Accordingly, we propose that PF11 should be considered as a potential agent for treating AD." @default.
• W2899200114 created "2018-11-09" @default.
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• W2899200114 date "2018-12-05" @default.
• W2899200114 modified "2023-10-13" @default.
• W2899200114 title "Pseudoginsenoside‐F11 alleviates oligomeric β‐amyloid‐induced endosome‐lysosome defects in microglia" @default.
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• W2899200114 doi "https://doi.org/10.1111/tra.12620" @default.
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