國家衛生研究院 NHRI:Item 3990099045/12510
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    题名: Post-treatment with posiphen reduces endoplasmic reticulum stress and neurodegeneration in stroke brain
    作者: Yu, SJ;Wu, KJ;Bae, E;Wang, YS;Chiang, CW;Kuo, LW;Harvey, BK;Greig, NH;Wang, Y
    贡献者: Center for Neuropsychiatric Research;Institute of Biomedical Engineering and Nanomedicine
    摘要: Acetylcholinesterase (AChE) inhibitors have protective and anti-inflammatory actions against brain injury, mediated by nicotinic alpha7 cholinergic receptor activation. The use of AChE inhibitors in patients is limited by systemic cholinergic side effects. Posiphen, a stereoisomer of the AChE inhibitor Phenserine, lacks AChE inhibitor activity. The purpose of this study is to determine the protective effect of Posiphen in cellular and animal models of stroke. Both Posiphen and Phenserine reduced glutamate-mediated neuronal loss in co-cultures of primary cortical cells and microglia. Phenserine-, but not Posiphen-, mediated neuroprotection was diminished by the nicotinic alpha7 receptor antagonist methyllycaconitine. Posiphen antagonized NMDA-mediated Ca(++) influx, thapsigargin-mediated neuronal loss and ER stress in cultured cells. Early post-treatment with Posiphen reduced ER stress signals, IBA1 immunoreactivity, TUNEL and infarction in the ischemic cortex, as well as neurological deficits in stroke rats. These findings indicate that Posiphen is neuroprotective against stroke through regulating Ca(++)i and ER stress.
    日期: 2020-02-21
    關聯: iScience. 2020 Feb 21;23(2):Article number 100866.
    Link to: http://dx.doi.org/10.1016/j.isci.2020.100866
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2589-0042&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000518637100048
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85078895434
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