RGD Reference Report - alpha1 Integrin activation: a link between beta-amyloid deposition and neuronal death in aging hippocampal neurons. - Rat Genome Database

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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.
RGD ID: 2302385
Pubmed: PMID:14991844   (View Abstract at PubMed)
DOI: DOI:10.1002/jnr.20018   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Itga1Ratpositive regulation of MAPK cascade  IMP hippocampal neurons in response to beta-amyloidRGD 
Itga1Ratpositive regulation of neuron apoptotic process  IMP hippocampal neurons in response to beta-amyloidRGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Itga1Ratexternal side of plasma membrane  IDA punctate staining of non-permeabilized hippocampal neuronsRGD 
Itga1Ratperikaryon  IDA diffuse staining in permeabilized hippocampal neurons RGD 

Objects Annotated

Genes (Rattus norvegicus)
Itga1  (integrin subunit alpha 1)


Additional Information