Beclin 1 mitigates motor and neuropathological deficits in genetic mouse models of Machado–Joseph disease
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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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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”
From Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival (2016) · cites this paper as [44]
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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
- Publisher
- Oxford University Press (OUP)
- 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
- bronze
- doi.org
- 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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