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Ginsenosides Decrease β-Amyloid Production via Potentiating Capacitative Calcium Entry
被引:2
作者:
Cho, Yoon Young
[1
]
Park, Jeong Hill
[2
]
Lee, Jung Hee
[3
]
Chung, Sungkwon
[1
]
机构:
[1] Sungkyunkwan Univ, Sch Med, Dept Physiol, Suwon 16419, South Korea
[2] Seoul Natl Univ, Res Inst Pharmaceut Sci, Coll Pharm, Seoul 08826, South Korea
[3] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Dept Radiol, Seoul 06351, South Korea
基金:
新加坡国家研究基金会;
关键词:
Alzheimer's disease;
Capacitative Ca2+entry;
Ginsenoside;
Amyloid beta-peptide;
Panax ginseng;
ALZHEIMERS-DISEASE;
COGNITIVE PERFORMANCE;
A-BETA;
GINSENG;
CHANNELS;
INHIBITION;
MODULATION;
MUTANTS;
DEFICIT;
D O I:
10.4062/biomolther.2023.172
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by extracellular amyloid plaques composed of amyloid beta-peptide (A beta). Studies have indicated that Ca2+ dysregulation is involved in AD pathology. It is reported that decreased capacitative Ca2+ entry (CCE), a refilling mechanism of intracellular Ca2+, resulting in increased A beta production. In contrast, constitutive activation of CCE could decrease A beta production. Panax ginseng Meyer is known to enhance memory and cognitive functions in healthy human subjects. We have previously reported that some ginsenosides decrease A beta levels in cultured primary neurons and AD mouse model brains. However, mechanisms involved in the A beta-lowering effect of ginsenosides remain unclear. In this study, we investigated the relationship between CCE and A beta production by examining the effects of various ginsenosides on CCE levels. A beta-lowering ginsenosides such as Rk1, Rg5, and Rg3 potentiated CCE. In contrast, ginsenosides without A beta-lowering effects (Re and Rb2) failed to potentiate CCE. The potentiating effect of ginsenosides on CCE was inhibited by the presence of 2-aminoethoxydiphenyl borate (2APB), an inhibitor of CCE. 2APB alone increased A beta 42 production. Furthermore, the presence of 2APB prevented the effects of ginsenosides on A beta 42 production. Our results indicate that ginsenosides decrease A beta production via potentiating CCE levels, confirming a close relationship between CCE levels and A beta production. Since CCE levels are closely related to A beta production, modulating CCE could be a novel target for AD therapeutics.
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页码:301 / 308
页数:8
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