ArticleScientific reports2019
Functional Transcriptome Analysis in ARSACS KO Cell Model Reveals a Role of Sacsin in Autophagy.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Cephalomannine as in vitro and in vivo anticancer agent in mesothelioma cells: mechanisms of action.BMC cancer · 2025Article
- Charlevoix-Saguenay spastic ataxia: a novel mutation in the SACS gene.Acta neurologica Belgica · 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
- 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
- Editorial: Translational research in hereditary spastic paraplegias: filling the diagnosis gap and therapeutic perspectives.Frontiers in neuroscience · 2025Article
- Altered Cellular Metabolism Is a Consequence of Loss of the Ataxia-Linked Protein Sacsin.International journal of molecular sciences · 2024Article
- Proteomics and lipidomic analysis reveal dysregulated pathways associated with loss of sacsin.Frontiers in neuroscience · 2024Article
- Autophagic lysosome reformation in health and disease.Autophagy · 2023Review
- In Vitro Characterization of Motor Neurons and Purkinje Cells Differentiated from Induced Pluripotent Stem Cells Generated from Patients with Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.Stem cells international · 2023Article
- Autosomal recessive cerebellar ataxias: a diagnostic classification approach according to ocular features.Frontiers in integrative neuroscience · 2023Article
- The J Domain of Sacsin Disrupts Intermediate Filament Assembly.International journal of molecular sciences · 2022Article
- Integrative Organelle-Based Functional Proteomics: In Silico Prediction of Impaired Functional Annotations inBiomolecules · 2022Article
- Transcriptomic characterization of tissues from patients and subsequent pathway analyses reveal biological pathways that are implicated in spastic ataxia.Cell & bioscience · 2022Article
- The interplay between oxidative stress and autophagy: focus on the development of neurological diseases.Behavioral and brain functions : BBF · 2022Review
- Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth.Scientific reports · 2021Article
- Efficient Neuroprotective Rescue of Sacsin-Related Disease Phenotypes in Zebrafish.International journal of molecular sciences · 2021Article
- A novel SACS p.Pro4154GlnfsTer20 mutation in a family with autosomal recessive spastic ataxia of Charlevoix-Saguenay.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Article
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9 authors.
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Abstract
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare early-onset neurological disease caused by mutations in SACS, which encodes sacsin. The complex architecture of sacsin suggests that it could be a key player in cellular protein quality control system. Molecular chaperones that operate in protein folding/unfolding and assembly/disassembly patterns have been described as essential modulators of selectivity during the autophagy process. We performed RNA-sequencing analysis to generate a whole-genome molecular signature profile of sacsin knockout cells. Using data analysis of biological processes significantly disrupted due to loss of sacsin, we confirmed the presence of decreased mitochondrial function associated with increased oxidative stress, and also provided a demonstration of a defective autophagic pathway in sacsin-depleted cells. Western blotting assays revealed decreased expression of LC3 and increased levels of p62 even after treatment with the lysosomal inhibitor bafilomycin A1, indicating impairment of the autophagic flux. Moreover, we found reduced co-immunolocalization of the autophagosome marker LC3 with lysosomal and mitochondrial markers suggesting fusion inhibition of autophagic compartments and subsequent failed cargo degradation, in particular failed degradation of damaged mitochondria. Pharmacological up-regulation of autophagy restored correct autophagic flux in sacsin knockout cells. These results corroborate the hypothesis that sacsin may play a role in autophagy. Chemical manipulation of this pathway might represent a new target to alleviate clinical and pathological symptoms, delaying the processes of neurodegeneration in ARSACS.
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