Cited by 97Genetic Neurodegenerative DiseasesAmyotrophic Lateral Sclerosis ResearchHereditary Neurological Disorders

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

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Nascimento-Ferreira, Isabel, Nóbrega, Clévio, Vasconcelos-Ferreira, Ana, Onofre, Isabel, Albuquerque, David, Aveleira, Célia, Hirai, Hirokazu, Déglon, Nicole +1 more·2013·Brain

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.

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Crossref · 10.1093/brain/awt144

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  • Over-expression of Beclin 1 significantly improves motor symptoms in a mouse model of Machado-Joseph disease or spinocerebellar ataxia type 3.

    “over-expression of Beclin 1 significantly improves motor symptoms in a mouse model of Machado-Joseph disease or spinocerebellar ataxia type 344”

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Authors
Nascimento-Ferreira, I., Nóbrega, C., Vasconcelos-Ferreira, A., Onofre, I., Albuquerque, D., Aveleira, C., Hirai, H., Déglon, N., & Pereira de Almeida, L.
Affiliations
  • Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
  • Centro de Neurociências e Biologia Celular (PT)
  • University of Coimbra (PT)
  • Gunma University (JP)
  • Centre Hospitalier Universitaire Vaudois (CH)
Venue
Brain
Published
2013-06-22
Volume
136
Issue
7
Pages
2173-2188
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
OpenAlex
W2159217600
Cited by
96
References
44
Citations by year
2026: 3 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 13 · 2020: 9 · 2019: 9 · 2018: 13 · 2017: 10 · 2016: 8 · 2015: 6 · 2014: 7 · 2013: 1
FWCI
3.59
Type
journal article
Language
en
Open access
Locations
  • Brain (publishedVersion)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (publishedVersion, other-oa)
  • reroDoc Digital Library (submittedVersion)
  • IRIS (submittedVersion)
Funders
  • National Ataxia Foundation
  • Fundação para a Ciência e a Tecnologia (SFRH/BD/61461/2009, SFRH/BD/29479/2006, PTDC/SAU-NEU/099307/2008, SFRH/BPD/73942/2010)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Keywords
Beclin-1, spinocerebellar ataxia type 3, ataxin-3, polyglutamine expansion, autophagy, lentiviral gene therapy, motor coordination, cerebellar ataxia, Purkinje cells, neurodegeneration, protein aggregation, transgenic mouse model
MeSH terms
Ataxin-3, Beclin-1, Age Factors, Analysis of Variance, Animals, Animals, Newborn, Autophagy, Cells, Cultured, Cerebellum, Disease Models, Animal, Postural Balance, Female, Gene Expression Regulation, Humans, Male, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity, Nerve Degeneration, Nerve Tissue Proteins, Nuclear Proteins, Peptides, Psychomotor Performance, Repressor Proteins, Sensation Disorders, Transfection, Machado-Joseph Disease, Green Fluorescent Proteins, Apoptosis Regulatory Proteins, Mice, Dopamine and cAMP-Regulated Phosphoprotein 32

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