Amentoflavone Promotes Cellular Uptake and Degradation of Amyloid-Beta in Neuronal Cells

Amentoflavone Promotes Cellular Uptake and Degradation of Amyloid-Beta in Neuronal Cells

Deposition of fibrillar forms of amyloid β-protein (Aβ) is commonly found in patients with Alzheimer's disease (AD) associated with cognitive decline. Impaired clearance of Aβ species is thought to be a major cause of late-onset sporadic AD. Aβ secreted into the extracellular milieu can be clea...

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Bibliographic Details
Published in:International journal of molecular sciences Vol. 23; no. 11; p. 5885
Main Authors: Han, Byung Hee, Cofell, Brooke, Everhart, Emily, Humpal, Courtney, Kang, Sam-Sik, Lee, Sang Kook, Kim-Han, Jeong Sook
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 24-05-2022
MDPI
Subjects:
Alzheimer disease
Alzheimer's disease
amyloid-beta clearance
Amyloidogenesis
Cell death
cellular uptake
Cognitive ability
Cytotoxicity
Endocytosis
Extracellular matrix
flavonoids
Heparan sulfate
Internalization
Lysosomes
neurodegeneration
Neurotoxicity
Peptides
Proteins
Scavenger receptors
polyphenols
drug discovery
Alzheimer disease
amyloid-beta clearance
neurodegeneration
flavonoids
cellular uptake
scavenger receptors
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Summary:Deposition of fibrillar forms of amyloid β-protein (Aβ) is commonly found in patients with Alzheimer's disease (AD) associated with cognitive decline. Impaired clearance of Aβ species is thought to be a major cause of late-onset sporadic AD. Aβ 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 Aβ remain to be tested. In the present study, we demonstrated that AMF significantly increased the cellular uptake of both Aβ and Aβ , but not inverted Aβ in mouse neuronal N2a cells. Though AMF promoted internalization of cytotoxic Aβ , it significantly reduced cell death in our assay condition. Our data further revealed that the internalized Aβ is translocated to lysosomes and undergoes enzymatic degradation. The saturable kinetic of Aβ 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 Aβ by increasing their cellular uptake and clearance, suggesting the therapeutic potential of AMF for the treatment of AD.
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content type line 23
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23115885