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CNS Neurosci Ther. 2017 Jun;23(6):526-534. doi: 10.1111/cns.12699. Epub 2017 Apr 21.

α-Mangostin decreases β-amyloid peptides production via modulation of amyloidogenic pathway.

Author information

1
Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
2
Center for Cellular Immunotherapy, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
3
Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

AIMS:

β-amyloid (Aβ) aggregation and deposition play a central role in the pathogenic process of Alzheimer's disease (AD). α-Mangostin (α-M), a polyphenolic xanthone, have been shown to dissociate Aβ oligomers. In this study, we further investigated the effect of α-M on Aβ production and its molecular mechanism.

METHODS:

The Aβ and soluble amyloid precursor protein α (sAPPα) in culture medium of cortical neurons were measured by ELISA. The activities of α-, β-, and γ-secretases were assayed, and the interaction between α-M and β- or γ-secretases was simulated by molecular docking.

RESULTS:

α-M significantly decreased Aβ40 and Aβ42 production. α-M did not affect the expression of enzymes involved in nonamyloidogenic and amyloidogenic pathways, but significantly decreased the activities of β-secretase and likely γ-secretase with IC50 13.22 nmol·L-1 and 16.98 nmol·L-1 , respectively. Molecular docking demonstrated that α-M interacted with β-site amyloid precursor protein cleaving enzyme 1 and presenilin 1 to interfere with their active sites.

CONCLUSIONS:

Our data demonstrate that α-M decreases Aβ production through inhibiting activities of β-secretase and likely γ-secretase in the amyloidogenic pathway. The current data together with previous study indicated that α-M could be a novel neuroprotective agent through intervention of multiple pathological processes of AD.

KEYWORDS:

Alzheimer's disease; α-mangostin; β-amyloid; β-secretase; γ-secretase

PMID:
28429536
DOI:
10.1111/cns.12699
[Indexed for MEDLINE]

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