کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
922038 1473937 2013 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Insulin-degrading enzyme deficiency accelerates cerebrovascular amyloidosis in an animal model
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Insulin-degrading enzyme deficiency accelerates cerebrovascular amyloidosis in an animal model
چکیده انگلیسی

Cerebrovascular amyloidosis (CA) may result in intraparenchymal bleeding and cognitive impairment. It was previously shown that transforming growth factor-β1 (TGF-β1) expression under an astrocyte promoter resulted in congophilic vascular deposits and vascular pathology. A reduction in insulin-degrading enzyme (IDE) activity was previously suggested to play a role in the accumulation of congophilic vascular deposits in the microvasculature of Alzheimer’s disease (AD) cases. Here, we aim to investigate the link between TGF-β1 and IDE activity in the development of CA. We found that TGF-β1 can reduce IDE expression in a mouse brain endothelial cell line (ECs). Furthermore, we discovered that IDE activity in the brains of TGF-β1 transgenic (Tg) mice was significantly reduced compared with that of the control mice in an age-dependent manner. In addition, TGF-β1/IDE−/− mice showed significantly greater levels of cerebrovascular pathology compared with TGF-β1 mice. We have previously shown that 16-month-old TGF-β1 mice have a significant reduction in synaptophysin protein levels, which may lead to cognitive impairment. Here we discovered a significant reduction in synaptophysin protein already at the age of seven in the hippocampus of TGF-β1/IDE−/− mice compared with TGF-β1 mice. Further investigation of TGF-β1–mediated IDE activity in ECs may provide useful therapeutic intervention targets for cerebrovascular diseases such as CA.


► TGF-β1 can reduce insulin degrading enzyme expression in mouse brain endothelial cell resulting in cerebrovascular amyloidosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain, Behavior, and Immunity - Volume 30, May 2013, Pages 143–149
نویسندگان
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