Inhibition of acetylcholinesterase activity and β‑amyloid oligomer formation by 6‑bromotryptamine A, a multi‑target anti‑Alzheimer's molecule

Jin,Xiaofeng; Wang,Minjun; Shentu,Jieyi; Huang,Chunhui; Bai,Yujing; Pan,Hanbo; Zhang,Difan; Yuan,Zhijun; Zhang,Hui; Xiao,Xiao; Wu,Xiang; Ding,Lijian; Wang,Qinwen; He,Shan; Cui,Wei

doi:10.3892/ol.2019.11226

Inhibition of acetylcholinesterase activity and β‑amyloid oligomer formation by 6‑bromotryptamine A, a multi‑target anti‑Alzheimer's molecule

Authors:
- Xiaofeng Jin
- Minjun Wang
- Jieyi Shentu
- Chunhui Huang
- Yujing Bai
- Hanbo Pan
- Difan Zhang
- Zhijun Yuan
- Hui Zhang
- Xiao Xiao
- Xiang Wu
- Lijian Ding
- Qinwen Wang
- Shan He
- Wei Cui
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Affiliations: Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China, Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China, Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Ningbo University, Ningbo, Zhejiang 315211, P.R. China
Published online on: December 18, 2019 https://doi.org/10.3892/ol.2019.11226
Pages: 1593-1601

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Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by learning and memory impairments. Recent studies have suggested that AD can be induced by multiple factors, such as cholinergic system dysfunction and β‑amyloid (Aβ) neurotoxicity. It was reported that 6‑bromo‑N‑propionyltryptamine could treat neurological diseases, including AD. In the present study, 6‑bromotryptamine A, a derivative of 6‑bromo‑N‑propionyltryptamine, was synthesized by the condensation of 2‑(6‑bromo‑1H‑indol‑3‑yl)ethan‑1‑amine and 2‑(4‑bromophenyl)acetic acid, and was used as a potential anti‑AD molecule. Furthermore, scopolamine can induce impairments of learning and memory, and was widely used to establish AD animal models. The results demonstrated that 6‑bromotryptamine A significantly prevented scopolamine‑induced short‑term cognitive impairments, as revealed by various behavioral tests in mice. Furthermore, an acetylcholinesterase (AChE) activity assay revealed that 6‑bromotryptamine A directly inhibited AChE activity. Notably, it was observed that 6‑bromotryptamine A blocked the formation of Aβ oligomer, as evaluated by the dot blot assay. All these results suggested that 6‑bromotryptamine A may be used to prevent impairments in short‑term learning and memory ability possibly via the inhibition of AChE and the blockade of Aβ oligomer formation.

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