NO-flurbiprofen reduces amyloid-beta, is neuroprotective in cell culture, and enhances cognition in response to cholinergic blockade.
NO-flurbiprofen reduces amyloid-beta, is neuroprotective in cell culture, and enhances cognition in response to cholinergic blockade.
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DOI：
10.1111/j.1471-4159.2009.06353.x
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发表时间：
2009-11
影响因子：
4.7
通讯作者：
Thatcher GR
中科院分区：
文献类型：
--
作者：
Abdul-Hay SO;Luo J;Ashghodom RT;Thatcher GR
The nonsteroidal anti-inflamatory drug (NSAID) flurbiprofen is a selective amyloid lowering agent (SALA) which has been studied clinically in Alzheimer’s disease. HCT-1026 is an ester prodrug of flurbiprofen incorporating a nitrate carrier moiety that in vivo provides NO bioactivity and an improved safety profile. In vitro, HCT-1026 retained the COX inhibitory and NSAID activity of flurbiprofen, but at concentrations at which levels of Aβ1–42 were lowered by flurbiprofen, Aβ1–42 levels were elevated 200% by HCT-1026. Conversely, at lower concentrations, HCT-1026 behaved as a SALA with greater potency than flurbiprofen. The difference in concentration responses between flurbiprofen and HCT-1026 in vitro suggests different cellular targets; and in no case did a combination of nitrate drug with flurbiprofen provide similar actions. In vivo, HCT-1026 was observed to reverse cognitive deficits induced by scopolamine in two behavioral assays; activity that was also shown by a classical nitrate drug, but not by flurbiprofen. The ability to restore aversive memory and spatial working and reference memory after cholinergic blockade has been demonstrated by other agents that stimulate NO/cGMP signaling. These observations add positively to the preclinical profile of HCT-1026 and NO chimeras in Alzheimer’s disease.
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影响因子：
4.8
作者：
Bhat, NR;Feinstein, DL;Bhat, AN
通讯作者：
Bhat, AN
影响因子：
2.9
作者：
Hauss-Wegrzyniak, B;Willard, LB;Wenk, GL
通讯作者：
Wenk, GL
影响因子：
2.1
作者：
Galasko, Douglas R.;Graff-Radford, Neil;Koo, Edward H.
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Koo, Edward H.
影响因子：
3.3
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Furlan, R;Kurne, A;Martino, G
通讯作者：
Martino, G
影响因子：
9.9
作者：
Breitner, J. C. S.;Haneuse, S. J. P. A.;Larson, E. B.
通讯作者：
Larson, E. B.