期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 30, 期 -, 页码 143-149出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2012.12.003
关键词
Alzheimer's disease; Cerebrovascular disease; Insulin-degrading enzyme; Endothelial cells; TGF-beta 1
资金
- Alzheimer's association
- ISF legacy [1092/11]
Cerebrovascular amyloidosis (CA) may result in intraparenchymal bleeding and cognitive impairment. It was previously shown that transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1 and IDE activity in the development of CA. We found that TGF-beta 1 can reduce IDE expression in a mouse brain endothelial cell line (ECs). Furthermore, we discovered that IDE activity in the brains of TGF-beta 1 transgenic (Tg) mice was significantly reduced compared with that of the control mice in an age-dependent manner. In addition, TGF-beta 1/IDE-/- mice showed significantly greater levels of cerebrovascular pathology compared with TGF-beta 1 mice. We have previously shown that 16-month-old TGF-beta 1 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-beta 1/IDE-/- mice compared with TGF-beta 1 mice. Further investigation of TGF-beta 1-mediated IDE activity in ECs may provide useful therapeutic intervention targets for cerebrovascular diseases such as CA. 2012 Elsevier Inc. All rights reserved.
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