کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6806600 | 1433573 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Selective benefits of simvastatin in bitransgenic APPSwe,Ind/TGF-β1 mice
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
Cognitive and cerebrovascular deficits are 2 landmarks of Alzheimer's disease (AD) to target for effective therapy. Here, we evaluated the efficacy of simvastatin in bitransgenic A/T mice overexpressing a mutated form of the human amyloid precursor protein (APPSwe,Ind) and a constitutively active form of transforming growth factor-β1. These mice feature the AD amyloid beta (Aβ) and cerebrovascular pathology. Simvastatin significantly decreased insoluble Aβ peptide levels and Aβ plaque load despite no effect on β-site amyloid precursor protein-cleaving enzyme and Aβ-degrading enzyme neprilysin protein levels. However, simvastatin failed to improve spatial learning and memory deficits and the decreased baseline levels of the memory-related protein early growth response-1 (Egr-1) in the hippocampus CA1 area. The impaired hyperemic response to whisker stimulation in A/T mice was not improved with treatment, but simvastatin fully restored constitutive nitric oxide synthesis in vessel walls and exacerbated agonist-mediated dilatory deficits. These findings point to the efficacy of simvastatin on selective AD features in a complex model of the disease, likely reflecting the challenges faced by recent clinical trials in assessing statin efficacy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 35, Issue 1, January 2014, Pages 203-212
Journal: Neurobiology of Aging - Volume 35, Issue 1, January 2014, Pages 203-212
نویسندگان
Panayiota Papadopoulos, Xin-Kang Tong, Edith Hamel,