Linked Life Data

17569064

Source:http://linkedlifedata.com/resource/pubmed/id/17569064

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-6-26
pubmed:abstractText
Neurodegenerative disorders share a process of aggregation of insoluble protein. Frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) is characterized by the presence of ubiquitin and TDP-43 positive aggregates which are likely related to specific gene expression profiles. We carried out gene expression microarray analysis on post-mortem brain tissue from FTLD-U, FTLD-MND, and controls. Using total RNA from carefully dissected frontal cortical layer II, we obtained gene expression profiles showing that FTLD-U and controls differ in over 100 networks, including those involved in synapse formation, the ubiquitin-proteasome system, endosomal sorting, and apoptosis. We performed qRT-PCR validation for three genes, representative of three different networks. Dynein axonemal light intermediate chain 1 (DNALI1) (microtubule/cytoskeleton network associated) expression was 3-fold higher and myeloid differentiation primary response gene 88 (MYD88) (signal transduction network) was 3.3 times higher in FTLD-U than FTLD-MND and controls; annexin A2 (ANXA2) (endosomal sorting) expression was 11.3-fold higher in FTLD-U than FTLD-MND and 2.3-fold higher than controls. The identification of progranulin (PGRN) gene mutations and TDP-43 as the major protein component of the ubiquitinated inclusions, are two recent landmark discoveries in the field of FTLD-U. We found 1.5-fold increase in TDP-43 in both FTLD-MND and FTLD-U while progranulin showed no gene expression differences between controls and FTLD-MND. However, one of the FTLD-U cases tested by Affymetrix microarray showed "absence call" of this transcript, suggesting absent or decreased gene expression. Our findings point to specific gene-linked-pathways which may be influenced by neurodegenerative disease process and may be targeted for further exploration.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0001-6322
pubmed:author
pubmed:issnType
Print
pubmed:volume
114
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
81-94
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17569064-Aged, pubmed-meshheading:17569064-Annexin A2, pubmed-meshheading:17569064-Axonemal Dyneins, pubmed-meshheading:17569064-Case-Control Studies, pubmed-meshheading:17569064-DNA-Binding Proteins, pubmed-meshheading:17569064-Dementia, pubmed-meshheading:17569064-Dyneins, pubmed-meshheading:17569064-Female, pubmed-meshheading:17569064-Gene Expression Profiling, pubmed-meshheading:17569064-Gene Expression Regulation, pubmed-meshheading:17569064-Humans, pubmed-meshheading:17569064-Inclusion Bodies, pubmed-meshheading:17569064-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:17569064-Male, pubmed-meshheading:17569064-Middle Aged, pubmed-meshheading:17569064-Motor Neuron Disease, pubmed-meshheading:17569064-Myeloid Differentiation Factor 88, pubmed-meshheading:17569064-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:17569064-Ubiquitin
pubmed:year
2007
pubmed:articleTitle
Gene expression analysis of frontotemporal lobar degeneration of the motor neuron disease type with ubiquitinated inclusions.
pubmed:affiliation
Cognitive Neurology and Alzheimer Disease Center, Northwestern University, Feinberg School of Medicine, 320 East Superior St, Chicago, IL, 60611, USA. manjari@northwestern.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural