Linked Life Data

21147772

Source:http://linkedlifedata.com/resource/pubmed/id/21147772

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-2-7
pubmed:abstractText
We have previously shown that overexpressing subunits of the iron-binding protein ferritin can rescue the toxicity of the amyloid ? (A?) peptide in our Drosophila model system. These data point to an important pathogenic role for iron in Alzheimer disease. In this study, we have used an iron-selective chelating compound and RNAi-mediated knockdown of endogenous ferritin to further manipulate iron in the brain. We confirm that chelation of iron protects the fly from the harmful effects of A?. To understand the pathogenic mechanisms, we have used biophysical techniques to see how iron affects A? aggregation. We find that iron slows the progression of the A? peptide from an unstructured conformation to the ordered cross-? fibrils that are characteristic of amyloid. Finally, using mammalian cell culture systems, we have shown that iron specifically enhances A? toxicity but only if the metal is present throughout the aggregation process. These data support the hypothesis that iron delays the formation of well ordered aggregates of A? and so promotes its toxicity in Alzheimer disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4248-56
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Iron promotes the toxicity of amyloid beta peptide by impeding its ordered aggregation.
pubmed:affiliation
Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/Medical Research Council Building, Hills Road, Cambridge CB2 0XY, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't