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Nisoli, I., Chauvin, J.P., Napoletano, F., Calamita, P., Zanin, V., Fanto, M., Charroux, B. (2010). Neurodegeneration by polyglutamine Atrophin is not rescued by induction of autophagy.  Cell Death Differ. 17(10): 1577--1587.
FlyBase ID
FBrf0212035
Publication Type
Research paper
Abstract

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.

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The fine line between waste disposal and recycling: DRPLA fly models illustrate the importance of completing the autophagy cycle for rescuing neurodegeneration.
Charroux and Fanto, 2010, Autophagy 6(5): 667--669 [FBrf0216354]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Death Differ.
    Title
    Cell Death and Differentiation
    Publication Year
    1994-
    ISBN/ISSN
    1350-9047
    Data From Reference