KMID : 0606920190270030276
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Biomolecules & Therapeutics 2019 Volume.27 No. 3 p.276 ~ p.282
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Justicidin A Reduces ¥â-Amyloid via Inhibiting Endocytosis of ¥â-Amyloid Precursor Protein
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Chun Yoon-Sun
Kwon Oh-Hoon Oh Hyun-Geun Cho Yoon-Young Yang Hyun-Ok Chung Sung-Kwon
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Abstract
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¥â-amyloid precursor protein (APP) can be cleaved by ¥á-, and ¥ã-secretase at plasma membrane producing soluble ectodomain fragment (sAPP¥á). Alternatively, following endocytosis, APP is cleaved by ¥â-, and ¥ã-secretase at early endosomes generating ¥â-amyloid (A¥â), the main culprit in Alzheimer¡¯s disease (AD). Thus, APP endocytosis is critical for A¥â production. Recently, we reported that Monsonia angustifolia, the indigenous vegetables consumed in Tanzania, improved cognitive function and decreased A¥â production. In this study, we examined the underlying mechanism of justicidin A, the active compound of M. angustifolia, on A¥â production. We found that justicidin A reduced endocytosis of APP, increasing sAPP¥á level, while decreasing A¥â level in HeLa cells overexpressing human APP with the Swedish mutation. The effect of justicidin A on A¥â production was blocked by endocytosis inhibitors, indicating that the decreased APP endocytosis by justicidin A is the underlying mechanism. Thus, justicidin A, the active compound of M. angustifolia, may be a novel agent for AD treatment.
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KEYWORD
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Alzheimer¡¯s disease, ¥â-amyloid precursor protein, Justicidin A, Endocytosis, ¥â-amyloid
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