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Aberrant expressions of pathogenic phenotype in Alzheimer's diseased transgenic mice carrying NSE-controlled APPsw

Title
Aberrant expressions of pathogenic phenotype in Alzheimer's diseased transgenic mice carrying NSE-controlled APPsw
Authors
Hwang D.Y.Cho J.S.Lee S.H.Chae K.R.Lim H.J.Min S.H.Seo S.J.Song Y.S.Song C.W.Paik S.G.Sheen Y.Y.Kim Y.K.
Ewha Authors
신윤용
SCOPUS Author ID
신윤용scopus
Issue Date
2004
Journal Title
Experimental Neurology
ISSN
0014-4886JCR Link
Citation
vol. 186, no. 1, pp. 20 - 32
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Mutations in the APP gene lead to enhanced cleavage by the β- and γ-secretase, and increased Aβ formation, which are tightly associated with Alzheimer's disease (AD)-like neuropathological changes. To examine whether depositions of Aβ by APP mutations are increased, and if this is associated with potential pathogenic phenotypes, the APPsw was expressed in a transgenic line under the control of the neuron-specific enolase (NSE) promoter. A behavioral dysfunction was shown at 12 months, and intensive staining bands, with APP and Aβ-42 antibodies, were visible in the brains of transgenic mice. Of the MAPK family, both JNK and p38 were activated in the brains of transgenic mice, whereas there was no significant activation of the ERK. In parallel, tau phosphorylation was also enhanced in the transgenic relative to the control mice. Moreover, the Cox-2 levels, from Western blot and immunostaining, were increased in the brains of the transgenic line. Furthermore, there were significant caspase-3- and TUNEL-stained nuclei in the transgenic line compared to the age-matched control mice. Thus, these results suggest that NSE-controlled APPsw transgenic mice appear to be a more relevant model in neuropathological phenotypes of AD, and thus could be useful in developing new therapeutic treatments for targeting the aberrant phenotypes that appear in these mice. © 2004 Elsevier Inc. All rights reserved.
DOI
10.1016/j.expneurol.2003.09.021
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약학대학 > 약학과 > Journal papers
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