Dieckol Ameliorates Aβ Production via PI3K/Akt/GSK-3β Regulated APP Processing in SweAPP N2a Cell
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 p...
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MDPI AG
2021-03-01
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| author | Jeong-Hyun Yoon Nayoung Lee Kumju Youn Mi Ra Jo Hyeung-Rak Kim Dong-Seok Lee Chi-Tang Ho Mira Jun |
| author_facet | Jeong-Hyun Yoon Nayoung Lee Kumju Youn Mi Ra Jo Hyeung-Rak Kim Dong-Seok Lee Chi-Tang Ho Mira Jun |
| author_sort | Jeong-Hyun Yoon |
| collection | DOAJ |
| description | 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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| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T13:13:35Z |
| publishDate | 2021-03-01 |
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| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-83f16eda2d594e1c8e8f329b8f59be062023-11-21T10:35:22ZengMDPI AGMarine Drugs1660-33972021-03-0119315210.3390/md19030152Dieckol Ameliorates Aβ Production via PI3K/Akt/GSK-3β Regulated APP Processing in SweAPP N2a CellJeong-Hyun Yoon0Nayoung Lee1Kumju Youn2Mi Ra Jo3Hyeung-Rak Kim4Dong-Seok Lee5Chi-Tang Ho6Mira Jun7Department of Health Sciences, The graduate School of Dong-A University, Busan 49315, KoreaDepartment of Health Sciences, The graduate School of Dong-A University, Busan 49315, KoreaDepartment of Food Science and Nutrition, Dong-A University, Busan 49315, KoreaDivision of Food Safety and Processing Research, National Institute of Fisheries Science, Busan 46083, KoreaDepartment of Food Science and Nutrition, Pukyong National University, Busan 48513, KoreaSchool of Life Sciences & Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 41566, KoreaDepartment of Food Science, Rutgers University, New Brunswick, NJ 08901, USADepartment of Health Sciences, The graduate School of Dong-A University, Busan 49315, KoreaThe 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.https://www.mdpi.com/1660-3397/19/3/152Alzheimer’s diseaseamyloid-beta peptideGSK-3βdieckolSweAPP N2a |
| spellingShingle | Jeong-Hyun Yoon Nayoung Lee Kumju Youn Mi Ra Jo Hyeung-Rak Kim Dong-Seok Lee Chi-Tang Ho Mira Jun Dieckol Ameliorates Aβ Production via PI3K/Akt/GSK-3β Regulated APP Processing in SweAPP N2a Cell Marine Drugs Alzheimer’s disease amyloid-beta peptide GSK-3β dieckol SweAPP N2a |
| title | Dieckol Ameliorates Aβ Production via PI3K/Akt/GSK-3β Regulated APP Processing in SweAPP N2a Cell |
| title_full | Dieckol Ameliorates Aβ Production via PI3K/Akt/GSK-3β Regulated APP Processing in SweAPP N2a Cell |
| title_fullStr | Dieckol Ameliorates Aβ Production via PI3K/Akt/GSK-3β Regulated APP Processing in SweAPP N2a Cell |
| title_full_unstemmed | Dieckol Ameliorates Aβ Production via PI3K/Akt/GSK-3β Regulated APP Processing in SweAPP N2a Cell |
| title_short | Dieckol Ameliorates Aβ Production via PI3K/Akt/GSK-3β Regulated APP Processing in SweAPP N2a Cell |
| title_sort | dieckol ameliorates aβ production via pi3k akt gsk 3β regulated app processing in sweapp n2a cell |
| topic | Alzheimer’s disease amyloid-beta peptide GSK-3β dieckol SweAPP N2a |
| url | https://www.mdpi.com/1660-3397/19/3/152 |
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