Linked Life Data

20339376

Source:http://linkedlifedata.com/resource/pubmed/id/20339376

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2010-9-13
pubmed:abstractText
Polyglutamine pathologies are neurodegenerative diseases that manifest both general polyglutamine toxicity and mutant protein-specific effects. Dentatorubral-pallidoluysian Atrophy (DRPLA) is one of these disorders caused by mutations in the Atrophin-1 protein. We have generated several models for DRPLA in Drosophila and analysed the mechanisms of cellular and organism toxicity. Our genetic and ultrastructural analysis of neurodegeneration suggests that autophagy may have a role in cellular degeneration when polyglutamine proteins are overexpressed in neuronal and glial cells. Clearance of autophagic organelles is blocked at the lysosomal level after correct fusion between autophagosomes and lysosomes. This leads to accumulation of autofluorescent pigments and proteinaceous residues usually degraded by the autophagy-lysosome system. Under these circumstances, further pharmacological and genetic induction of autophagy does not rescue neurodegeneration by polyglutamine Atrophins, in contrast to many other neurodegenerative conditions. Our data thus provide a crucial insight into the specific mechanism of a polyglutamine disease and reveal important differences in the role of autophagy with respect to other diseases of the same family.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1476-5403
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1577-87
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Neurodegeneration by polyglutamine Atrophin is not rescued by induction of autophagy.
pubmed:affiliation
Dulbecco Telethon Institute and Division of Neuroscience, DIBIT-San Raffaele Scientific Institute, Via Olgettina 58, Milan I-20132, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't