Linked Life Data

12025818

Source:http://linkedlifedata.com/resource/pubmed/id/12025818

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-5-23
pubmed:abstractText
The amyloid beta-peptide (Abeta) is a 39-43 residue amphipathic peptide that is the major proteinaceous component of senile plaques that are characteristic of Alzheimer's disease (AD). To examine the contribution of the hydrophobic carboxyl-terminal domain on the aggregation, fibril formation, and neurotoxic activity, we have examined the effect of substituting the carboxyl-terminal residues 29-42 derived from two other type I transmembrane proteins: the beta-adrenergic and low-density lipoprotein (LDL) receptor. The chimeric peptides, Abeta1-28ADR29-42 and Abeta1-28LDL29-42, have the same high beta-sheet content as human Abeta1-42 in solution at pH 7.4 and display a conformation-dependent epitope that is associated with Abeta aggregates, indicating that these properties are largely independent of the carboxyl domain sequence. Previous studies have shown that the length of the carboxyl terminus is important for the formation of sodium dodecyl sulfate (SDS)-resistant oligomers. Abeta1-42 and the chimeric peptides co-assemble to form SDS-resistant, oligomeric mixed aggregates in all permutations, indicating that this interaction is not sequence specific. Upon assembly into insoluble aggregates, both chimeric peptides display an amorphous morphology rather than the regular 6-10 nm fibrils that are typical of human Abeta1-42. Abeta1-28ADR29-42 is equally toxic to primary rat hippocampal neurons as Abeta1-42, while Abeta1-28LDL29-42 is devoid of toxic activity. These results indicate that although beta-sheet conformation may be required for toxic activity, it is not sufficient and 6-10 nm fibril morphology is not an obligate requirement for neuronal toxicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1535-1084
pubmed:author
pubmed:issnType
Print
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
81-94
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
The influence of the carboxyl terminus of the Alzheimer Abeta peptide on its conformation, aggregation, and neurotoxic properties.
pubmed:affiliation
Department of Molecular Biology and Bichemistry, University of California, Irvine, CA 92697-3900, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.