Meserine, a novel carbamate AChE inhibitor, ameliorates scopolamine-induced dementia and alleviates amyloidogenesis of APP/PS1 transgenic mice

Bi Yun Shao, Zheng Xia, Qiong Xie, Xin Xing Ge, Wei Wei Zhang, Jian Sun, Pan Jiang, Hao Wang, Wei Dong Le, Zhui Bai Qiu, Yang Lu, Hong Zhuan Chen

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Aims: To investigate whether Meserine, a novel phenylcarbamate derivative of (-)-meptazinol, possesses beneficial activities against cholinergic deficiency and amyloidogenesis, the two major pathological characteristics of Alzheimer's disease (AD). Methods: Ellman's assay and Morris water maze were used to detect acetylcholinesterase (AChE) activity and evaluate spatial learning and memory ability, respectively. Both high content screening and Western blotting were carried out to detect β-amyloid precursor protein (APP), while RT-PCR and ELISA were conducted to detect APP-mRNA and β-amyloid peptide (Aβ). Results: In scopolamine-induced dementia mice, Meserine (1 mg/kg, i.p.) significantly ameliorated spatial learning and memory deficits, which was consistent with its in vitro inhibitory ability against AChE (recombinant human AChE, IC50 = 274 ± 49 nM). Furthermore, Meserine (7.5 mg/kg) injected intraperitoneally once daily for 3 weeks lowered APP level by 28% and Aβ42 level by 42% in APP/PS1 transgenic mouse cerebrum. This APP modulation action might be posttranscriptional, as Meserine reduced APP by about 30% in SH-SY5Y-APP695 cells but did not alter APP-mRNA level. And both APP and Aβ42 lowering action of Meserine maintained longer than that of rivastigmine. Conclusion: Meserine executes dual actions against cholinergic deficiency and amyloidogenesis and provides a promising lead compound for symptomatic and modifying therapy of AD.

Original languageEnglish (US)
Pages (from-to)165-171
Number of pages7
JournalCNS Neuroscience and Therapeutics
Volume20
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • β-amyloid peptide
  • β-amyloid precursor protein
  • AChE inhibitor
  • Alzheimer's disease
  • Meserine

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Physiology (medical)
  • Psychiatry and Mental health
  • Pharmacology

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