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Meserine, a novel carbamate AChE inhibitor, ameliorates scopolamine-induced dementia and alleviates amyloidogenesis of APP/PS1 transgenic mice.
CNS Neurosci Ther. 2014 Feb; 20(2):165-71.CN

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.

Authors+Show Affiliations

Department of Pharmacology & Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24279603

Citation

Shao, Bi-Yun, et al. "Meserine, a Novel Carbamate AChE Inhibitor, Ameliorates Scopolamine-induced Dementia and Alleviates Amyloidogenesis of APP/PS1 Transgenic Mice." CNS Neuroscience & Therapeutics, vol. 20, no. 2, 2014, pp. 165-71.
Shao BY, Xia Z, Xie Q, et al. Meserine, a novel carbamate AChE inhibitor, ameliorates scopolamine-induced dementia and alleviates amyloidogenesis of APP/PS1 transgenic mice. CNS Neurosci Ther. 2014;20(2):165-71.
Shao, B. Y., Xia, Z., Xie, Q., Ge, X. X., Zhang, W. W., Sun, J., Jiang, P., Wang, H., Le, W. D., Qiu, Z. B., Lu, Y., & Chen, H. Z. (2014). Meserine, a novel carbamate AChE inhibitor, ameliorates scopolamine-induced dementia and alleviates amyloidogenesis of APP/PS1 transgenic mice. CNS Neuroscience & Therapeutics, 20(2), 165-71. https://doi.org/10.1111/cns.12183
Shao BY, et al. Meserine, a Novel Carbamate AChE Inhibitor, Ameliorates Scopolamine-induced Dementia and Alleviates Amyloidogenesis of APP/PS1 Transgenic Mice. CNS Neurosci Ther. 2014;20(2):165-71. PubMed PMID: 24279603.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Meserine, a novel carbamate AChE inhibitor, ameliorates scopolamine-induced dementia and alleviates amyloidogenesis of APP/PS1 transgenic mice. AU - Shao,Bi-Yun, AU - Xia,Zheng, AU - Xie,Qiong, AU - Ge,Xin-Xing, AU - Zhang,Wei-Wei, AU - Sun,Jian, AU - Jiang,Pan, AU - Wang,Hao, AU - Le,Wei-Dong, AU - Qiu,Zhui-Bai, AU - Lu,Yang, AU - Chen,Hong-Zhuan, Y1 - 2013/11/27/ PY - 2013/05/23/received PY - 2013/09/09/revised PY - 2013/09/09/accepted PY - 2013/11/28/entrez PY - 2013/11/28/pubmed PY - 2014/9/10/medline KW - AChE inhibitor KW - Alzheimer's disease KW - Meserine KW - β-amyloid peptide KW - β-amyloid precursor protein SP - 165 EP - 71 JF - CNS neuroscience & therapeutics JO - CNS Neurosci Ther VL - 20 IS - 2 N2 - 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. SN - 1755-5949 UR - https://www.unboundmedicine.com/medline/citation/24279603/Meserine_a_novel_carbamate_AChE_inhibitor_ameliorates_scopolamine_induced_dementia_and_alleviates_amyloidogenesis_of_APP/PS1_transgenic_mice_ L2 - https://doi.org/10.1111/cns.12183 DB - PRIME DP - Unbound Medicine ER -