Linked Life Data

21062285

Source:http://linkedlifedata.com/resource/pubmed/id/21062285

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-12-20
pubmed:abstractText
TAR DNA-binding protein-43 (TDP-43) proteinopathy has been linked to several neurodegenerative diseases, such as frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. Phosphorylated and ubiquitinated TDP-43 C-terminal fragments have been found in cytoplasmic inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis patients. However, the factors and pathways that regulate TDP-43 aggregation are still not clear. We found that the C-terminal 15 kDa fragment of TDP-43 is sufficient to induce aggregation but the aggregation phenotype is modified by additional sequences. Aggregation is accompanied by phosphorylation at serine residues 409/410. Mutation of 409/410 to phosphomimetic aspartic acid residues significantly reduces aggregation. Inhibition of either proteasome or autophagy dramatically increases TDP-43 aggregation. Furthermore, TDP-43 aggregates colocalize with markers of autophagy and the adaptor protein p62/SQSTM1. Over-expression of p62/SQSTM1 reduces TDP-43 aggregation in an autophagy and proteasome-dependent manner. These studies suggest that aggregation of TDP-43 C-terminal fragments is regulated by phosphorylation events and both the autophagy and proteasome-mediated degradation pathways.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1471-4159
pubmed:author
pubmed:copyrightInfo
© 2010 The Authors. Journal of Neurochemistry © 2010 International Society for Neurochemistry.
pubmed:issnType
Electronic
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
248-59
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Regulation of TDP-43 aggregation by phosphorylation and p62/SQSTM1.
pubmed:affiliation
Weill Institute for Cell and Molecular Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't