期刊
TRANSLATIONAL PSYCHIATRY
卷 3, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/tp.2012.147
关键词
A beta(1-42); neuronal death program; Rac 1 GTPase
类别
资金
- Carlos III Health Institute (Spanish Ministry of Science and Innovation) [CD06/00275]
- Programa IKERTU, Department of Industry of the Basque Country Government
- Spanish Ministry of Science and Innovation [CIT-300000-2008-8]
- Department of Industry of the Basque Country Government [S-PE11UN018]
- University of the Basque Country [EHU11/08, UFI 11/20]
1-42 beta-Amyloid (A beta(1-42)) peptide is a key molecule involved in the development of Alzheimer's disease. Some of its effects are manifested at the neuronal morphological level. These morphological changes involve loss of neurites due to cytoskeleton alterations. However, the mechanism of A beta(1-42) peptide activation of the neurodegenerative program is still poorly understood. Here, A beta(1-42) peptide-induced transduction of cellular death signals through the phosphatidylinositol 3-kinase (PI3K)/phosphoinositol- dependent kinase (PDK)/novel protein kinase C (nPKC)/Rac 1 axis is described. Furthermore, pharmacological inhibition of PDK1 and nPKC activities blocks Rac 1 activation and neuronal cell death. Our results provide insights into an unsuspected connection between PDK1, nPKCs and Rac 1 in the same signal-transduction pathway and points out nPKCs and Rac 1 as potential therapeutic targets to block the toxic effects of A beta(1-42) peptide in neurons. Translational Psychiatry (2013) 3, e219; doi:10.1038/tp.2012.147; published online 22 January 2013
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据