AI Article Synopsis
- The study focuses on how the processing of amyloid precursor protein (APP) leads to amyloid-β peptide (Aβ) accumulation, a contributing factor in Alzheimer's disease.
- Among the three phlorotannins tested, dieckol was identified as the most effective in reducing both intra- and extracellular Aβ levels by regulating key enzymes involved in APP processing.
- Dieckol also promotes the activation of the PI3K/Akt signaling pathway, which helps in the inhibition of GSK-3β, further contributing to the reduction of Aβ production.
Article Abstract
The proteolytic processing of amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase releases amyloid-β peptide (Aβ), which deposits in amyloid plaques and contributes to the initial causative events of Alzheimer's disease (AD). In the present study, the regulatory mechanism of APP processing of three phlorotannins was elucidated in Swedish mutant APP overexpressed N2a (SweAPP N2a) cells. Among the tested compounds, dieckol exhibited the highest inhibitory effect on both intra- and extracellular Aβ accumulation. In addition, dieckol regulated the APP processing enzymes, such as α-secretase (ADAM10), β-secretase, and γ-secretase, presenilin-1 (PS1), and their proteolytic products, sAPPα and sAPPβ, implying that the compound acts on both the amyloidogenic and non-amyloidogenic pathways. In addition, dieckol increased the phosphorylation of protein kinase B (Akt) at Ser473 and GSK-3β at Ser9, suggesting dieckol induced the activation of Akt, which phosphorylated GSK-3β. The specific phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 triggered GSK-3β activation and Aβ expression. In addition, co-treatment with LY294002 noticeably blocked the effect of dieckol on Aβ production, demonstrating that dieckol promoted the PI3K/Akt signaling pathway, which in turn inactivated GSK-3β, resulting in the reduction in Aβ levels.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001366 | PMC |
| http://dx.doi.org/10.3390/md19030152 | DOI Listing |
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