Biomol Ther.  2019 May;27(3):276-282. 10.4062/biomolther.2018.112.

Justicidin A Reduces β-Amyloid via Inhibiting Endocytosis of β-Amyloid Precursor Protein

• Chun YS
• Kwon OH
• Oh HG
• Cho YY
• Yang HO
• Chung S

• KMID: 2447854
• DOI: http://doi.org/10.4062/biomolther.2018.112

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.

Keyword

Alzheimer's disease; β-amyloid precursor protein; Justicidin A; Endocytosis; β-amyloid

MeSH Terms

Alzheimer Disease
Cell Membrane
Cognition
Endocytosis*
Endosomes
HeLa Cells
Humans
Tanzania
Vegetables