کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6021899 | 1580654 | 2014 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Neuroprotective role of MMP-9 overexpression in the brain of Alzheimer's 5xFAD mice
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Accumulation of amyloid-β (Îβ) peptide is believed to play a central role in the pathogenesis of Alzheimer's disease (AD). Lowering Aβ levels in the brain may thus improve synaptic and cognitive deficits observed in AD patients. In the non-amyloidogenic pathway, the amyloid-β precursor protein (APP) is cleaved within the Aβ peptide sequence by α-secretases, giving rise to the potent neurotrophic N-terminal fragment sÎPPα. We have previously reported that gelatinase B/matrix metalloproteinase 9 (MMP-9), a matrix metalloproteinase critically involved in neuronal plasticity, acts as α-secretase both in vitro and in vivo and reduces Aβ levels in vitro. In the present study, we demonstrate that neuronal overexpression of MMP-9 in a transgenic AD mouse model harboring five familial AD-related mutations (5xFAD) resulted in increased sAPPα levels and decreased Aβ oligomers without affecting amyloid plaque load in the brain. Functionally, overexpression of MMP-9 prevented the cognitive deficits displayed by 5xFAD mice, an improvement that was accompanied by increased levels of the pre-synaptic protein synaptophysin and mature brain-derived neurotrophic factor (BDNF) in the brain. These results suggest that in vivo activation of endogenous MMP-9 could be a promising target for interference with development and/or progression of AD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 70, October 2014, Pages 179-189
Journal: Neurobiology of Disease - Volume 70, October 2014, Pages 179-189
نویسندگان
Apostolia Fragkouli, Effie C. Tsilibary, Athina K. Tzinia,