ArticleBrain : a journal of neurology2016
Unbiased screen identifies aripiprazole as a modulator of abundance of the polyglutamine disease protein, ataxin-3.
Article in Brain : a journal of neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Blood DDIT4 and TRIM13 Transcript Levels Mark the Early Stages of Machado-Joseph Disease.Annals of neurology · 2025Article
- Therapeutic Effects ofInternational journal of molecular sciences · 2025Article
- Spinocerebellar Ataxia Type 3 Pathophysiology-Implications for Translational Research and Clinical Studies.International journal of molecular sciences · 2024Review
- High throughput compound screening in neuronal cells identifies statins as activators of ataxin 3 expression.Scientific reports · 2023Article
- Endurance exercise ameliorates phenotypes ineLife · 2022Article
- Aripiprazole Offsets Mutant ATXN3-Induced Motor Dysfunction by Targeting Dopamine DBiomedicines · 2022Article
- Ubiquitin-binding site 1 of pathogenic ataxin-3 regulates its toxicity inFrontiers in neuroscience · 2022Article
- Targeting the VCP-binding motif of ataxin-3 improves phenotypes in Drosophila models of Spinocerebellar Ataxia Type 3.Neurobiology of disease · 2021Article
- New Perspectives of Gene Therapy on Polyglutamine Spinocerebellar Ataxias: From Molecular Targets to Novel Nanovectors.Pharmaceutics · 2021Review
- Mutant Ataxin-3-Containing Aggregates (MATAGGs) in Spinocerebellar Ataxia Type 3: Dynamics of the Disorder.Molecular neurobiology · 2021Review
- Druggable genome screen identifies new regulators of the abundance and toxicity of ATXN3, the Spinocerebellar Ataxia type 3 disease protein.Neurobiology of disease · 2020Article
- Recent Advances in the Treatment of Cerebellar Disorders.Brain sciences · 2019Review
- Differential toxicity of ataxin-3 isoforms in Drosophila models of Spinocerebellar Ataxia Type 3.Neurobiology of disease · 2019Article
- Drug screens ofDisease models & mechanisms · 2019Article
- From Pathogenesis to Novel Therapeutics for Spinocerebellar Ataxia Type 3: Evading Potholes on the Way to Translation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Antisense oligonucleotide therapy rescues aggresome formation in a novel spinocerebellar ataxia type 3 human embryonic stem cell line.Stem cell research · 2019Article
- Unanchored ubiquitin chains do not lead to marked alterations in gene expression inBiology open · 2019Article
- Citalopram Reduces Aggregation of ATXN3 in a YAC Transgenic Mouse Model of Machado-Joseph Disease.Molecular neurobiology · 2019Article
- Spinocerebellar ataxias: prospects and challenges for therapy development.Nature reviews. Neurology · 2018Review
- Insights into C9ORF72-Related ALS/FTD from Drosophila and iPSC Models.Trends in neurosciences · 2018Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
No disease-modifying treatment exists for the fatal neurodegenerative polyglutamine disease known both as Machado-Joseph disease and spinocerebellar ataxia type 3. As a potential route to therapy, we identified small molecules that reduce levels of the mutant disease protein, ATXN3. Screens of a small molecule collection, including 1250 Food and Drug Administration-approved drugs, in a novel cell-based assay, followed by secondary screens in brain slice cultures from transgenic mice expressing the human disease gene, identified the atypical antipsychotic aripiprazole as one of the hits. Aripiprazole increased longevity in a Drosophila model of Machado-Joseph disease and effectively reduced aggregated ATXN3 species in flies and in brains of transgenic mice treated for 10 days. The aripiprazole-mediated decrease in ATXN3 abundance may reflect a complex response culminating in the modulation of specific components of cellular protein homeostasis. Aripiprazole represents a potentially promising therapeutic drug for Machado-Joseph disease and possibly other neurological proteinopathies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.