Abstract:
:We have previously designed and synthesized a series of novel memantine nitrates, and some of them have shown neuroprotective effects; however, the detailed mechanisms remain unknown. In this study, we demonstrated that MN-12, one of the memantine nitrates, concentration-dependently protected against glutamate-induced neurotoxicity in rat primary cultured cerebellar granule neurons (CGNs). Western blotting assays revealed that MN-12 might possess neuroprotective effects through the inhibition of ERK pathway and activation of PI3K/Akt pathway concurrently. Moreover, MN-12 concentration-dependently dilated precontracted rat middle cerebral artery through activation of NO-cGMP pathway ex vivo. In the 2-vessel occlusion (2VO) rat model, MN-12 alleviated the impairments of spatial memory and motor dysfunction possibly via neuroprotection and improvement of the cerebral blood flow. Furthermore, the results of preliminary pharmacokinetic studies showed that MN-12 might quickly distribute to the major organs including the brain, indicating that MN-12 could penetrate the blood-brain barrier. Taken together, MN-12 might provide multifunctional therapeutic benefits for dementia associated with Alzheimer's disease, vascular dementia, and ischemic stroke, via neuroprotection and vessel dilation to improve the cerebral blood flow.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Mak S,Liu Z,Wu L,Guo B,Luo F,Liu Z,Hu S,Wang J,Cui G,Sun Y,Wang Y,Zhang G,Han Y,Zhang Zdoi
10.1021/acschemneuro.9b00242subject
Has Abstractpub_date
2020-02-05 00:00:00pages
314-327issue
3issn
1948-7193journal_volume
11pub_type
杂志文章abstract::Extensive experimental and computational studies have suggested that multiple Zn(2+) binding modes in amyloid β (Aβ) peptides could exist simultaneously. However, consistent results have not been obtained for the effects of Zn(2+) binding on Aβ structure, dynamics, and kinetics in particular. Some key questions such a...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
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journal_title:ACS chemical neuroscience
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journal_title:ACS chemical neuroscience
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn5000953
更新日期:2014-10-15 00:00:00
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.6b00142
更新日期:2016-11-16 00:00:00
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn400079y
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn4000814
更新日期:2013-05-15 00:00:00
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn400077d
更新日期:2013-08-21 00:00:00
abstract::Aβ peptides, the main protein components of Alzheimer's disease (AD) plaques, derive from a proteolytic cleavage of the amyloid precursor protein. Due to heterogeneous cleavage sites, a series of Aβ peptides, including the major and widely studied species Aβ1-40 (Aβ40) and Aβ1-42 (Aβ42), are produced. In addition to t...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.6b00456
更新日期:2017-04-19 00:00:00
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.8b00617
更新日期:2019-03-20 00:00:00
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00078
更新日期:2017-09-20 00:00:00
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journal_title:ACS chemical neuroscience
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
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更新日期:2013-05-15 00:00:00
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journal_title:ACS chemical neuroscience
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更新日期:2012-10-17 00:00:00
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.0c00386
更新日期:2020-10-21 00:00:00
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.0c00519
更新日期:2021-01-27 00:00:00
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章
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abstract::A series of bimodal metabotropic glutamate-receptor targeted MRI contrast agents has been developed and evaluated, based on established competitive metabotropic Glu receptor subtype 5 (mGluR5) antagonists. In order to directly visualize mGluR5 binding of these agents on the surface of live astrocytes, variations in th...
journal_title:ACS chemical neuroscience
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journal_title:ACS chemical neuroscience
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更新日期:2018-08-15 00:00:00
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章
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