Linked Life Data

21527912

Source:http://linkedlifedata.com/resource/pubmed/id/21527912

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2011-6-1
pubmed:abstractText
Alzheimer's disease (AD) is the most common form of dementia and associated with progressive deposition of amyloid ?-peptides (A?) in the brain. A? derives by sequential proteolytic processing of the amyloid precursor protein by ?- and ?-secretases. Rare mutations that lead to amino-acid substitutions within or close to the A? domain promote the formation of neurotoxic A? assemblies and can cause early-onset AD. However, mechanisms that increase the aggregation of wild-type A? and cause the much more common sporadic forms of AD are largely unknown. Here, we show that extracellular A? undergoes phosphorylation by protein kinases at the cell surface and in cerebrospinal fluid of the human brain. Phosphorylation of serine residue 8 promotes formation of oligomeric A? assemblies that represent nuclei for fibrillization. Phosphorylated A? was detected in the brains of transgenic mice and human AD brains and showed increased toxicity in Drosophila models as compared with non-phosphorylated A?. Phosphorylation of A? could represent an important molecular mechanism in the pathogenesis of the most common sporadic form of AD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1460-2075
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2255-65
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Extracellular phosphorylation of the amyloid ?-peptide promotes formation of toxic aggregates during the pathogenesis of Alzheimer's disease.
pubmed:affiliation
Department of Neurology, University of Bonn, Bonn, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't