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Amentoflavone Promotes Cellular Uptake and Degradation of Amyloid-Beta in Neuronal Cells
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Cited 5 time in Scopus
- Authors
- Issue Date
- 2022-06
- Citation
- International Journal of Molecular Sciences, Vol.23 No.11, p. 5885
- Abstract
- Deposition of fibrillar forms of amyloid beta-protein (A beta) is commonly found in patients with Alzheimer's disease (AD) associated with cognitive decline. Impaired clearance of A beta species is thought to be a major cause of late-onset sporadic AD. A beta secreted into the extracellular milieu can be cleared from the brain through multiple pathways, including cellular uptake in neuronal and non-neuronal cells. Recent studies have showed that the naturally-occurring polyphenol amentoflavone (AMF) exerts anti-amyloidogenic effects. However, its effects on metabolism and cellular clearance of A beta remain to be tested. In the present study, we demonstrated that AMF significantly increased the cellular uptake of both A beta(1-40) and A beta(1-42), but not inverted A beta(42-1) in mouse neuronal N2a cells. Though AMF promoted internalization of cytotoxic A beta(1-42), it significantly reduced cell death in our assay condition. Our data further revealed that the internalized A beta is translocated to lysosomes and undergoes enzymatic degradation. The saturable kinetic of A beta uptake and our pharmacologic experiments showed the involvement of receptor-mediated endocytosis, in part, through the class A scavenger receptors as a possible mechanism of action of AMF. Taken together, our findings indicate that AMF can lower the levels of extracellular A beta by increasing their cellular uptake and clearance, suggesting the therapeutic potential of AMF for the treatment of AD.
- ISSN
- 1661-6596
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