کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6278538 | 1295823 | 2007 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by Aβ25-35
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
By means of i.c.v. administration of preaggregated oligomeric β-amyloid (Aβ)25-35 peptide it was possible in rats to generate neuropathological signs related to those of early stages of Alzheimer's disease (AD). Aβ25-35-administration induced the deposition of endogenously produced amyloid protein. Furthermore, quantitative immunohistochemistry demonstrated time-related statistically significant increases in amyloid immunoreactivity, tau phosphorylation, microglial activation, and astrocytosis, and stereological investigations demonstrated statistically significant increased neuronal cell death and brain atrophy in response to Aβ25-35. Finally, the Aβ25-35-administration led to a reduced short-term memory as determined by the social recognition test. A synthetic peptide termed FGL derived from the neural cell adhesion molecule (NCAM) was able to prevent or, if already manifest, strongly reduce all investigated signs of Aβ25-35-induced neuropathology and cognitive impairment. The FGL peptide was recently demonstrated to be able to cross the blood-brain-barrier. Accordingly, we found that the beneficial effects of FGL were achieved not only by intracisternal, but also by intranasal and s.c. administration of the peptide. Furthermore, FGL-treatment was shown to inhibit the activity of GSK3β, a kinase implicated in signaling regulating cell survival, tau phosphorylation and the processing of the amyloid precursor protein (APP). Thus, the peptide induced a statistically significant increase in the fraction of GSK3β phosphorylated on the Ser9-position, a posttranslational modification known to inhibit the activity of the kinase. Hence, the mode of action of FGL with respect to the preventive and curative effects on Aβ25-35-induced neuropathological manifestations and cognitive impairment involves the modulation of intracellular signal-transduction mediated through GSK3β.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 145, Issue 1, 2 March 2007, Pages 209-224
Journal: Neuroscience - Volume 145, Issue 1, 2 March 2007, Pages 209-224
نویسندگان
B. Klementiev, T. Novikova, V. Novitskaya, P.S. Walmod, O. Dmytriyeva, B. Pakkenberg, V. Berezin, E. Bock,