ArticleMolecular neurobiology2016
Parkin Protects Against Misfolded SOD1 Toxicity by Promoting Its Aggresome Formation and Autophagic Clearance.
Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- GPCR-Mediated Cell Intelligence: A Potential Mechanism for Survival and Long-Term Health.Current issues in molecular biology · 2026Review
- Ubiquitin signatures on aggregating proteins in neurodegeneration.Essays in biochemistry · 2025Review
- Divergent and convergent TMEM106B pathology in murine models of neurodegeneration and human disease.Acta neuropathologica communications · 2025Article
- Review
- Acetyl-L-carnitine and Amyotrophic Lateral Sclerosis: Current Evidence and Potential use.CNS & neurological disorders drug targets · 2024Review
- Autophagy and neurodegeneration: Unraveling the role of C9ORF72 in the regulation of autophagy and its relationship to ALS-FTD pathology.Frontiers in cellular neuroscience · 2023Review
- Protein clearance strategies for disease intervention.Journal of neural transmission (Vienna, Austria : 1996) · 2022Review
- Drosophila p38 MAPK interacts with BAG-3/starvin to regulate age-dependent protein homeostasis.Aging cell · 2021Article
- Ubiquitin signaling in neurodegenerative diseases: an autophagy and proteasome perspective.Cell death and differentiation · 2021Review
- Prevention of mitochondrial impairment by inhibition of protein phosphatase 1 activity in amyotrophic lateral sclerosis.Cell death & disease · 2020Article
- Primate differential redoxome (PDR) - A paradigm for understanding neurodegenerative diseases.Redox biology · 2020Article
- Defining novel functions for cerebrospinal fluid in ALS pathophysiology.Acta neuropathologica communications · 2020Review
- Cross-talk between redox signalling and protein aggregation.Biochemical Society transactions · 2020Review
- Causative Links between Protein Aggregation and Oxidative Stress: A Review.International journal of molecular sciences · 2019Review
- Article
- Structural Properties and Interaction Partners of Familial ALS-Associated SOD1 Mutants.Frontiers in neurology · 2019Review
- Bioenergetics and Autophagic Imbalance in Patients-Derived Cell Models of Parkinson Disease Supports Systemic Dysfunction in Neurodegeneration.Frontiers in neuroscience · 2019Review
- Repurposing carbamazepine for the treatment of amyotrophic lateral sclerosis in SOD1-G93A mouse model.CNS neuroscience & therapeutics · 2018Article
- Distinct multilevel misregulations of Parkin and PINK1 revealed in cell and animal models of TDP-43 proteinopathy.Cell death & disease · 2018Article
- Causative Genes in Amyotrophic Lateral Sclerosis and Protein Degradation Pathways: a Link to Neurodegeneration.Molecular neurobiology · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in Cu/Zn superoxide dismutase (SOD1) cause autosomal dominant amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease with no effective treatment. Despite ample evidence indicating involvement of mutation-induced SOD1 protein misfolding and aggregation in ALS pathogenesis, the molecular mechanisms that control cellular management of misfolded, aggregation-prone SOD1 mutant proteins remain unclear. Here, we report that parkin, an E3 ubiquitin-protein ligase which is linked to Parkinson's disease, is a novel regulator of cellular defense against toxicity induced by ALS-associated SOD1 mutant proteins. We find that parkin mediates K63-linked polyubiquitination of SOD1 mutants in cooperation with the UbcH13/Uev1a E2 enzyme and promotes degradation of these misfolded SOD1 proteins by the autophagy-lysosome system. In response to strong proteotoxic stress associated with proteasome impairment, parkin promotes sequestration of misfolded and aggregated SOD1 proteins to form perinuclear aggresomes, regulates positioning of lysosomes around misfolded SOD1 aggresomes, and facilitates aggresome clearance by autophagy. Our findings reveal parkin-mediated cytoprotective mechanisms against misfolded SOD1 toxicity and suggest that enhancing parkin-mediated cytoprotection may provide a novel therapeutic strategy for treating ALS.
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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.