Transforming growth factor-β1 potentiates amyloid-β generation in astrocytes and in transgenic mice
Transforming growth factor-β1 potentiates amyloid-β generation in astrocytes and in transgenic mice
复制标题
DOI：
10.1074/jbc.m300819200
复制
发表时间：
2003-05-16
影响因子：
4.8
通讯作者：
Vivien, D
中科院分区：
文献类型：
--
作者：
Lesné, S;Docagne, F;Vivien, D
Accumulation of the amyloid-beta peptide (Abeta) in the brain is crucial for development of Alzheimer's disease. Expression of transforming growth factor-beta1 (TGF-beta1), an immunosuppressive cytokine, has been correlated in vivo with Abeta accumulation in transgenic mice and recently with Abeta clearance by activated microglia. Here, we demonstrate that TGF-beta1 drives the production of Abeta40/42 by astrocytes leading to Abeta production in TGF-beta1 transgenic mice. First, TGF-beta1 induces the overexpression of the amyloid precursor protein (APP) in astrocytes but not in neurons, involving a highly conserved TGF-B1-responsive element in the 5'-untranslated region (+54/ +74) of the APP promotor. Second, we demonstrated an increased release of soluble APP-beta which led to TGF-beta1-induced Abeta generation in both murine and human astrocytes. These results demonstrate that TGF-beta1 potentiates Abeta production in human astrocytes and may enhance the formation of plaques burden in the brain of Alzheimer's disease patients.
