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alpha1 Integrin activation: a link between beta-amyloid deposition and neuronal death in aging hippocampal neurons.

Authors: Anderson, KL  Ferreira, A 
Citation: Anderson KL and Ferreira A, J Neurosci Res. 2004 Mar 1;75(5):688-97.
Pubmed: (View Article at PubMed) PMID:14991844
DOI: Full-text: DOI:10.1002/jnr.20018

A growing body of evidence obtained using in vitro model systems indicates that the deposition of fibrillar beta-amyloid (Abeta) results in neurite degeneration and cell death in central neurons. Little is known, however, about the molecular mechanisms underlying these neurotoxic effects. We have shown previously that fibrillar Abeta induced sustained activation of the mitogen-activated protein kinase (MAPK) followed by hyperphosphorylation of tau proteins in aging hippocampal neurons. Furthermore, the blockage of MAPK activation using specific inhibitors prevented neurite degeneration in these cells. These results suggested that the MAPK signal transduction pathway could play a key role in Abeta-induced neurite degeneration. We sought to identify upstream elements of the MAPK signaling cascade activated by Abeta deposition. We evaluated the participation of the integrins in this pathway by monitoring the activation of MAPK in the presence of specific integrin inhibitors. Our results indicate that pretreatment of mature hippocampal neurons with either echistatin or alpha(1) integrin-blocking antibodies prevented Abeta-induced MAPK activation. In addition, the blockage of alpha(1) activation prevented cell death induced by Abeta. Similar results were obtained when alpha(1) and beta(1) integrin blocking antibodies were used combined. Taken collectively, these results identify alpha(1) integrin and the alpha(1) plus beta(1) integrin complexes as potential targets for therapeutic intervention in the Abeta signaling pathway in aging neurons.


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CRRD Object Information
CRRD ID: 2302385
Created: 2008-12-15
Species: All species
Last Modified: 2008-12-15
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.