Linked Life Data

14991844

Source:http://linkedlifedata.com/resource/pubmed/id/14991844

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-3-1
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0360-4012
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
75
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
688-97
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
alpha1 Integrin activation: a link between beta-amyloid deposition and neuronal death in aging hippocampal neurons.
pubmed:affiliation
Institute for Neuroscience, Northwestern University, Chicago, Illinois 60611, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.