Linked Life Data

18187234

Source:http://linkedlifedata.com/resource/pubmed/id/18187234

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2009-7-20
pubmed:abstractText
Amyloid beta (Abeta) is a metabolic product of amyloid-beta precursor protein (APP). Deposition of Abeta in the brain and neuronal degeneration are characteristic hallmarks of Alzheimer's disease (AD). Abeta induces neuronal degeneration, but the mechanism of neurotoxicity remains elusive. Here we show that overexpression of APP renders hippocampal neurons vulnerable to Abeta toxicity. Deletion of the extracellular Abeta sequence of APP prevents binding of APP to Abeta, and abolishes toxicity. Abeta toxicity is also abrogated by deletion of the cytoplasmic domain of APP, or by deletions comprising the Go protein-binding sequence of APP. Treatment with Pertussis toxin (PTX) abrogates APP-dependent toxicity of Abeta. Overexpression of PTX-insensitive Galpha-o subunit, but not Galpha-i subunit, of G protein restores Abeta toxicity in the presence of PTX, and this requires the integrity of APP-binding site for Go protein. Altogether, these experiments indicate that interaction of APP with toxic Abeta-species promotes toxicity in hippocampal neurons by a mechanism that involves APP-mediated Go protein activation, revealing an Abeta-receptor-like function of APP directly implicated in neuronal degeneration in AD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1558-1497
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1379-92
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Amyloid-beta precursor protein mediates neuronal toxicity of amyloid beta through Go protein activation.
pubmed:affiliation
Instituto de Investigación Médica- CONICET, Córdoba, Argentina.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't