The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Amyloid-beta induces Smac release via AP-1/ Bim activation in cerebral endothelial cells.

Insoluble fibrils of amyloid-beta peptide (Abeta) are the major component of senile and vascular plaques found in the brains of Alzheimer's disease (AD) patients. Abeta has been implicated in neuronal and vascular degeneration because of its toxicity to neurons and endothelial cells in vitro; some of these cells die with characteristic features of apoptosis. We used primary cultures of murine cerebral endothelial cells (CECs) to explore the mechanisms involved in Abeta-induced cell death. We report here that Abeta(25-35), a cytotoxic fragment of Abeta, induced translocation of the apoptosis regulator termed second-mitochondria-derived activator of caspase (Smac) from the intramembranous compartment of the mitochondria to the cytosol 24 hr after exposure. In addition, we demonstrated that X chromosome-linked inhibitor-of-apoptosis protein (XIAP) coimmunoprecipitated with Smac, suggesting that the two proteins bound to one another subsequent to the release of Smac from the mitochondria. Abeta(25-35) treatment also led to rapid AP-1 activation and subsequent expression of Bim, a member of the BH3-only family of proapoptotic proteins. Bim knockdown using an antisense oligonucleotide strategy suppressed Abeta(25-35)-induced Smac release and resulted in attenuation of CEC death. Furthermore, AP-1 inhibition, with curcumin or c-fos antisense oligonucleotide, reduced bim expression. These results suggest that Abeta activates an apoptotic cascade involving AP-1 DNA binding, subsequent bim induction, followed by Smac release and binding to XIAP, resulting in CEC death.[1]


  1. Amyloid-beta induces Smac release via AP-1/Bim activation in cerebral endothelial cells. Yin, K.J., Lee, J.M., Chen, S.D., Xu, J., Hsu, C.Y. J. Neurosci. (2002) [Pubmed]
WikiGenes - Universities