Chun, Yoon Sun Kwon, Oh-Hoon Oh, Hyun Geun Cho, Yoon Young Yang, Hyun Ok Chung, Sungkwon 2024-01-19T20:03:48Z 2024-01-19T20:03:48Z 2021-09-02 2019-05 1976-9148 https://pubs.kist.re.kr/handle/201004/120053 beta-amyloid precursor protein (APP) can be cleaved by alpha-, and gamma-secretase at plasma membrane producing soluble ectodomain fragment (sAPP alpha). Alternatively, following endocytosis, APP is cleaved by beta-, and gamma-secretase at early endosomes generating beta-amyloid (A beta), the main culprit in Alzheimer's disease (AD). Thus, APP endocytosis is critical for A beta production. Recently, we reported that Monsonia angustifolia, the indigenous vegetables consumed in Tanzania, improved cognitive function and decreased A beta production. In this study, we examined the underlying mechanism of justicidin A, the active compound of M. angustifolia, on A beta production. We found that justicidin A reduced endocytosis of APP, increasing sAPPa level, while decreasing A beta level in HeLa cells overexpressing human APP with the Swedish mutation. The effect of justicidin A on A beta 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. English KOREAN SOC APPLIED PHARMACOLOGY ALPHA-SECRETASE CLEAVAGE O-GLYCOSYLATION IDENTIFICATION LOCALIZATION TRAFFICKING MECHANISMS GENERATION ECTODOMAIN RELEASE PATHWAY Justicidin A Reduces beta-Amyloid via Inhibiting Endocytosis of beta-Amyloid Precursor Protein Article 10.4062/biomolther.2018.112 1 BIOMOLECULES & THERAPEUTICS, v.27, no.3, pp.276 - + BIOMOLECULES & THERAPEUTICS 27 3 276 + scie scopus kci ART002460623 000468227600004 2-s2.0-85067806725 Biochemistry & Molecular Biology Pharmacology & Pharmacy Biochemistry & Molecular Biology Pharmacology & Pharmacy Article ALPHA-SECRETASE CLEAVAGE O-GLYCOSYLATION IDENTIFICATION LOCALIZATION TRAFFICKING MECHANISMS GENERATION ECTODOMAIN RELEASE PATHWAY Alzheimer&apos s disease beta-amyloid precursor protein Justicidin A Endocytosis beta-amyloid