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

多靶点抗阿尔茨海默病分子 6-溴色胺 A 抑制乙酰胆碱酯酶活性和 β-淀粉样蛋白寡聚体的形成

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作者: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

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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