ArticleProceedings of the National Academy of Sciences of the United States of America2012
Mitochondrial dysfunction and Purkinje cell loss in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 191 citations in OpenAlex.
- The recurrent SACS gene p.Arg272His hotspot expands the neurodevelopmental and cognitive spectrum of ARSACS.Neurogenetics · 2026Article
- Loss of SARM1 Improves Phenotypes in a Mouse Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.Neurology. Genetics · 2026Article
- Cerebellar deep brain stimulation rescues Purkinje cell mitochondrial density in a genetic mouse model of cerebellar ataxia.Brain research bulletin · 2026Article
- Synaptic mitochondrial dysfunction and Alzheimer's disease: from molecular mechanisms to therapeutic strategies.Frontiers in pharmacology · 2026Review
- Frameshift and Copy Number Variants inNeurology. Genetics · 2025Article
- S100B Mitigates Cytoskeletal and Mitochondrial Alterations in a Glial Cell Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.Molecular neurobiology · 2025Article
- Long-term benefits of TUDCA supplement in ARSACS zebrafish model.Scientific reports · 2025Article
- Decreased mitochondrial activity in the demyelinating cerebellum of progressive multiple sclerosis and chronic EAE contributes to Purkinje cell loss.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Alterations in the NaCerebellum (London, England) · 2025Article
- Modeling sacsin depletion in Danio Rerio offers new insight on retinal defects in ARSACS.Neurobiology of disease · 2025Article
- Whole Blood DNA Methylation Analysis Reveals Epigenetic Changes Associated with ARSACS.Cerebellum (London, England) · 2025Article
- ARSACS: Clinical Features, Pathophysiology and iPS-Derived Models.Cerebellum (London, England) · 2025Review
- Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay with Early-Onset Epilepsy and Novel Clinical Features:Sultan Qaboos University medical journal · 2025Article
- Altered Cellular Metabolism Is a Consequence of Loss of the Ataxia-Linked Protein Sacsin.International journal of molecular sciences · 2024Article
- Driving Mitochondrial Fission Improves Cognitive, but not Motor Deficits in a Mouse Model of Ataxia of Charlevoix-Saguenay.Cerebellum (London, England) · 2024Article
- An MRI evaluation of white matter involvement in paradigmatic forms of spastic ataxia: results from the multi-center PROSPAX study.Journal of neurology · 2024Article
- Article
- Compound Heterozygous Mutations ofInternational journal of molecular sciences · 2024Article
- Driving mitochondrial fission improves cognitive, but not motor deficits in a mouse model of Ataxia of Charlevoix-Saguenay.Research square · 2024Article
- Widening the clinical, radiological and genetic spectrum of autosomal recessive ataxia of Charlevoix-Saguenay in Indian patients.Acta neurologica Belgica · 2024Article
47 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
Abstract
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset neurological disease resulting from mutations in the SACS gene encoding sacsin, a 4,579-aa protein of unknown function. Originally identified as a founder disease in Québec, ARSACS is now recognized worldwide. Prominent features include pyramidal spasticity and cerebellar ataxia, but the underlying pathology and pathophysiological mechanisms are unknown. We have generated an animal model for ARSACS, sacsin knockout mice, that display age-dependent neurodegeneration of cerebellar Purkinje cells. To explore the pathophysiological basis for this observation, we examined the cell biological properties of sacsin. We show that sacsin localizes to mitochondria in non-neuronal cells and primary neurons and that it interacts with dynamin-related protein 1, which participates in mitochondrial fission. Fibroblasts from ARSACS patients show a hyperfused mitochondrial network, consistent with defects in mitochondrial fission. Sacsin knockdown leads to an overly interconnected and functionally impaired mitochondrial network, and mitochondria accumulate in the soma and proximal dendrites of sacsin knockdown neurons. Disruption of mitochondrial transport into dendrites has been shown to lead to abnormal dendritic morphology, and we observe striking alterations in the organization of dendritic fields in the cerebellum of knockout mice that precedes Purkinje cell death. Our data identifies mitochondrial dysfunction/mislocalization as the likely cellular basis for ARSACS and indicates a role for sacsin in regulation of mitochondrial dynamics.
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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.