Beclin 1 mitigates motor and neuropathological deficits in genetic mouse models of Machado-Joseph disease.

Details

Ressource 1Download: serval:BIB_3611C54A5E61.P001 (1537.86 [Ko])
State: Public
Version: author
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It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
Serval ID
serval:BIB_3611C54A5E61
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Beclin 1 mitigates motor and neuropathological deficits in genetic mouse models of Machado-Joseph disease.
Journal
Brain
Author(s)
Nascimento-Ferreira I., Nóbrega C., Vasconcelos-Ferreira A., Onofre I., Albuquerque D., Aveleira C., Hirai H., Déglon N., Pereira de Almeida L.
ISSN
1460-2156 (Electronic)
ISSN-L
0006-8950
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
136
Number
Pt 7
Pages
2173-2188
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
Machado-Joseph disease or spinocerebellar ataxia type 3, the most common dominantly-inherited spinocerebellar ataxia, results from translation of the polyglutamine-expanded and aggregation prone ataxin 3 protein. Clinical manifestations include cerebellar ataxia and pyramidal signs and there is no therapy to delay disease progression. Beclin 1, an autophagy-related protein and essential gene for cell survival, is decreased in several neurodegenerative disorders. This study aimed at evaluating if lentiviral-mediated beclin 1 overexpression would rescue motor and neuropathological impairments when administered to pre- and post-symptomatic lentiviral-based and transgenic mouse models of Machado-Joseph disease. Beclin 1-mediated significant improvements in motor coordination, balance and gait with beclin 1-treated mice equilibrating longer periods in the Rotarod and presenting longer and narrower footprints. Furthermore, in agreement with the improvements observed in motor function beclin 1 overexpression prevented neuronal dysfunction and neurodegeneration, decreasing formation of polyglutamine-expanded aggregates, preserving Purkinje cell arborization and immunoreactivity for neuronal markers. These data show that overexpression of beclin 1 in the mouse cerebellum is able to rescue and hinder the progression of motor deficits when administered to pre- and post-symptomatic stages of the disease.
Pubmed
Web of science
Open Access
Yes
Create date
04/08/2013 8:23
Last modification date
25/09/2019 6:08
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