Linked Life Data

19746990

Source:http://linkedlifedata.com/resource/pubmed/id/19746990

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2009-11-6
pubmed:abstractText
Neurodegenerative diseases are often defined pathologically by the presence of protein aggregates. These aggregates, including amyloid plaques in Alzheimer's disease (AD), result from the abnormal accumulation and processing of proteins, and may ultimately lead to neuronal dysfunction and cell death. To date, conventional biochemical studies have revealed abundant core components in protein aggregates. However, rapidly improving proteomics technologies offer opportunities to revisit pathologic aggregate composition, and to identify less abundant but potentially important functional molecules that participate in neurodegeneration. The purpose of this study was to establish a proteomic strategy for the profiling of neurodegenerative disease tissues for disease-specific changes in protein abundance. Using high resolution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), we analyzed detergent-insoluble frontal cortex samples from AD and unaffected control cases. In addition, we analyzed samples from frontotemporal lobar degeneration (FTLD) cases to identify AD-specific changes not present in other neurodegenerative diseases. We used a labeling-free quantification technique to compare the abundance of identified peptides in the samples based on extracted ion current (XIC) of their corresponding ions. Of the 512 identified proteins, quantitation demonstrated significant changes in 81 AD-specific proteins. Following additional manual filtering, 11 proteins were accepted with high confidence as increased in AD compared to control and FTLD brains, including beta-amyloid, tau and apolipoprotein E, all well-established AD-linked proteins. In addition, we identified and validated the presence of serine protease 15, ankyrin B, and 14-3-3 eta in the detergent-insoluble fraction. Our results provide further evidence for the capacity of proteomics applications to identify conserved sets of disease-specific proteins in AD, to enhance our understanding of disease pathogenesis, and to deliver new candidates for the development of effective therapies for this, and other, devastating neurodegenerative disorders.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1535-3907
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5069-79
pubmed:dateRevised
2010-12-3
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Proteomics analysis reveals novel components in the detergent-insoluble subproteome in Alzheimer's disease.
pubmed:affiliation
Department of Neurology, Emory University, Atlanta, Georgia 30322, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural