کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9943321 | 1573500 | 2005 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Perturbed Neurogenesis in the Adult Hippocampus Associated with Presenilin-1 A246E Mutation
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
In addition to its well-established role in γ-secretase cleavage, presenilin (PS) also plays a role in regulating the stability of cytosolic β-catenin, a protein involved in Wnt signaling. Several familial Alzheimer's disease-associated PS1 mutations have been shown to increase the stability of the signaling pool of β-catenin, correlating with enhanced cell proliferation. Accordingly, we hypothesized that in the setting of PS1 mutations, abnormal activation of Wnt/β-catenin signaling leads to increased cell division. We tested this hypothesis by examining whether there is evidence of increased neurogenesis in the hippocampus of adult transgenic mice that overexpress the PS1 A246E mutation. In PS1/PS2-deficient fibroblasts, expression of PS1 A246E Familial AD mutation failed to restore the rapid turnover of β-catenin compared with wild-type PS1. We then examined whether the same mutation enhanced neurogenesis in vivo in adult hippocampus of PS1-deficient mice when restored by wild-type human PS1 (PS1â/âWT) or A246E PS1 mutation (PS1â/âAE). The PS1 A246E mutation stimulated the proliferation of progenitor cells in the dentate gyrus of adult mice, as assessed by 5-bromo-2-deoxyuridine incorporation, but did not influence their survival or differentiation. These observations suggest that the PS1 A246E mutation influences cell growth putatively via abnormal β-catenin signaling in vivo.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The American Journal of Pathology - Volume 167, Issue 1, July 2005, Pages 151-159
Journal: The American Journal of Pathology - Volume 167, Issue 1, July 2005, Pages 151-159
نویسندگان
Nathalie L. Chevallier, Salvador Soriano, David E. Kang, Eliezer Masliah, Gloria Hu, Edward H. Koo,