Linked Life Data

16857350

Source:http://linkedlifedata.com/resource/pubmed/id/16857350

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2006-8-14
pubmed:abstractText
The CLN6 vLINCL is caused by molecular defects in CLN6 gene coding for an ER resident transmembrane protein whose function is unknown. In the present study gene expression profiling of CLN6-deficient fibroblasts using cDNA microarray was undertaken in order to provide novel insights into the molecular mechanisms underlying this neurodegenerative fatal disease. Data were validated by qRT-PCR. Statistically significant alterations of expression were observed for 12 transcripts. The two most overexpressed genes, versican and tissue factor pathway inhibitor 2, are related to extracellular matrix (ECM), predicting changes in ECM-related proteins in CLN6-deficient cells. Transcript profiling also suggested alterations in signal transduction pathways, apoptosis and the immune/inflammatory response. Up-regulated genes related to steroidogenesis or signalling, and the relationship between cholesterol dynamics and glycosphingolipid sorting, led to investigation of free cholesterol and gangliosides in CLN6-deficient fibroblasts. Cholesterol accumulation in lysosomes suggests a homeostasis block as a result of CLN6p deficiency. The cholesterol imbalance may affect structure/function of caveolae and lipid rafts, disrupting signalling transduction pathways and sorting cell mechanisms. Alterations in protein/lipid intracellular trafficking would affect the composition and function of endocytic compartments, including lysosomes. Dysfunctional endosomal/lysosomal vesicles may act as one of the triggers for apoptosis and cell death, and for a secondary protective inflammatory response. In conclusion, the data reported provide novel clues into molecular pathophysiological mechanisms of CLN6-deficiency, and may also help in developing disease biomarkers and therapies for this and other neurodegenerative diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:volume
1762
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
637-46
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Gene expression profiling in vLINCL CLN6-deficient fibroblasts: Insights into pathobiology.
pubmed:affiliation
Unidade de Enzimologia, Instituto de Genética Médica Jacinto Magalhães, Porto, Portugal.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't