A Erkner

AM Cuervo

B Charroux

B Ravikumar

C Settembre

CA Ross

CI Holmberg

D Kretzschmar

E Romero

ES Emamian

F Napoletano

FC Nucifora Jr

G Bjorkoy

G Schilling

H Naito

HK Chen

I Nisoli

IP Nezis

J P Chauvin

JC Lievens

JD Wood

JL Marsh

JM Warrick

JS Karres

JS Steffan

JS Zoltewicz

K Venkatachalam

M Arrasate

M Degtyarev

M Fanto

M Razi

M Yamada

N Mizushima

P Calamita

P Venkatraman

RA Nixon

RC Hardie

RC Scott

S Boillee

S Montrasio

S Nagafuchi

S Sarkar

S Zhang

SK Custer

T Sato

T Tamura

T Wang

V Zanin

Y Hayashi

Y Shen

Z Berger

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. Cell Death and Differentiation (2010) 17, 1577-1587; doi:10.1038/cdd.2010.31; published online 26 March 201

Nisoli, I.

Chauvin, J. P.

Napoletano, F.

Calamita, P.

Zanin, V.

Fanto, M.

Charroux, B.

King's Research Portal

Neurodegeneration by polyglutamine Atrophin is not rescued by induction of autophagy

International audiencePolyglutamine pathologies are neurodegenerative diseases that manifest both general polyglutamine toxicity and mutant protein specific effects. Dentatorubropallidoluysian 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 have analysed the mechanisms of cellular and organism toxicity. Our genetic and ultrastructural analysis of neurodegeneration suggests may play a role in cellular degeneration when polyQ 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 autofluorecent pigments and of proteinaceous residues usually degraded by the autophagy-lysosome system. In these circumstances, further pharmacological and genetic induction of autophagy does not rescue neurodegeneration by polyQ 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

Fanto, Manolis

Nisoli, Ilaria

Chauvin, Jean Paul

Napoletano, Francesco

Calamita, Piera

Zanin, Valentina

Charroux, Bernard

HAL: Hyper Article en Ligne

J. P., Chauvin

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

Archivio istituzionale della ricerca - Università di Trieste

HAL AMU

Hal-Diderot

https://hal.science/hal-00521164v1/document

Neurodegeneration by polyglutamine Atrophin is not rescued by induction of autophagy

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HAL: Hyper Article en Ligne

HAL: Hyper Article en Ligne

Archivio istituzionale della ricerca - Università di Trieste

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Hal-Diderot