Biomol Ther  
Justicidin A Reduces β-Amyloid via Inhibiting Endocytosis of β-Amyloid Precursor Protein
Yoon Sun Chun1,2, Oh-Hoon Kwon1, Hyun Geun Oh1, Yoon Young Cho1, Hyun Ok Yang2,3,* and Sungkwon Chung1,*
1Department of Physiology, Sungkyunkwan University School of Medicine, Suwon 16419,
2Natural Products Research Center, Korea Institute of Science and Technology, Gangneung 25451,
3Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea
E-mail: schung@skku.edu (Chung S), hoyang@kist.re.kr (Yang HO)
Tel: +82-31-299-6103 (Chung S), +82-33-650-3501 (Yang HO)
Fax: +82-31-299-6129 (Chung S), +82-33-650-3529 (Yang HO)
Received: June 19, 2018; Revised: August 8, 2018; Accepted: September 1, 2018; Published online: October 11, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
β-amyloid precursor protein (APP) can be cleaved by α-, and γ-secretase at plasma membrane producing soluble ectodomain fragment (sAPPα). Alternatively, following endocytosis, APP is cleaved by β-, and γ-secretase at early endosomes generating β-amyloid (Aβ), the main culprit in Alzheimer’s disease (AD). Thus, APP endocytosis is critical for Aβ production. Recently, we reported that Monsonia angustifolia, the indigenous vegetables consumed in Tanzania, improved cognitive function and decreased Aβ production. In this study, we examined the underlying mechanism of justicidin A, the active compound of M. angustifolia, on Aβ production. We found that justicidin A reduced endocytosis of APP, increasing sAPPα level, while decreasing Aβ level in HeLa cells overexpressing human APP with the Swedish mutation. The effect of justicidin A on Aβ 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.
Keywords: Alzheimer’s disease, β-amyloid precursor protein, Justicidin A, Endocytosis, β-amyloid


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