ArticleExperimental neurology2012
Ubiquitin proteasome system in Parkinson's disease: a keeper or a witness?
Article in Experimental neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Profiling peripheral immune cells in Parkinson's disease: A scoping review.Journal of Parkinson's disease · 2026Review
- Neurodegeneration models in Parkinson's disease: cellular and molecular paths to neuron death.Behavioral and brain functions : BBF · 2025Review
- Autophagy and UPS pathway contribute to nicotine-induced protection effect in Parkinson's disease.Experimental brain research · 2024Article
- Lack of Parkinsonian Pathology and Neurodegeneration in Mice After Long-Term Injections of a Proteasome Inhibitor in Olfactory Bulb and Amygdala.Frontiers in aging neuroscience · 2021Article
- Fatty Acid Binding Protein 5 Mediates Cell Death by Psychosine Exposure through Mitochondrial Macropores Formation in Oligodendrocytes.Biomedicines · 2020Article
- Mechanistic Interplay Between Autophagy and Apoptotic Signaling in Endosulfan-Induced Dopaminergic Neurotoxicity: Relevance to the Adverse Outcome Pathway in Pesticide Neurotoxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- The Protective Effect of Repeated 1MeTIQ Administration on the Lactacystin-Induced Impairment of Dopamine Release and Decline in TH Level in the Rat Brain.Neurotoxicity research · 2018Article
- Upregulation of PSMB8 and cathepsins in the human brains of dementia with Lewy bodies.Neuroscience letters · 2018Article
- Stem Cell Transplantation and Physical Exercise in Parkinson's Disease, a Literature Review of Human and Animal Studies.Stem cell reviews and reports · 2018Review
- Parkinson's Disease: Biomarkers, Treatment, and Risk Factors.Frontiers in neuroscience · 2018Review
- In utero delivery of rAAV2/9 induces neuronal expression of the transgene in the brain: towards new models of Parkinson's disease.Gene therapy · 2017Article
- Genetic Analysis of FBXO2, FBXO6, FBXO12, and FBXO41 Variants in Han Chinese Patients with Sporadic Parkinson's Disease.Neuroscience bulletin · 2017Article
- Expanded and Wild-type Ataxin-3 Modify the Redox Status of SH-SY5Y Cells Overexpressing α-Synuclein.Neurochemical research · 2017Article
- The Proteasome Inhibition Model of Parkinson's Disease.Journal of Parkinson's disease · 2017Review
- Sorting out release, uptake and processing of alpha-synuclein during prion-like spread of pathology.Journal of neurochemistry · 2016Review
- Inhibition of Protein Ubiquitination by Paraquat and 1-Methyl-4-Phenylpyridinium Impairs Ubiquitin-Dependent Protein Degradation Pathways.Molecular neurobiology · 2016Article
- Linking F-box protein 7 and parkin to neuronal degeneration in Parkinson's disease (PD).Molecular brain · 2016Review
- TOPORS, a Dual E3 Ubiquitin and Sumo1 Ligase, Interacts with 26 S Protease Regulatory Subunit 4, Encoded by the PSMC1 Gene.PloS one · 2016Article
- The Upshot of LRRK2 Inhibition to Parkinson's Disease Paradigm.Molecular neurobiology · 2015Article
- Age-related changes in the proteostasis network in the brain of the naked mole-rat: Implications promoting healthy longevity.Biochimica et biophysica acta · 2015Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveThe aim of this work was to evaluate the role of ubiquitin-proteasome system (UPS) on mitochondrial-driven alpha-synuclein (aSN) clearance in in vitro, ex vivo and in vivo Parkinson's disease (PD) cellular models.
methodWe used SH-SY5Y ndufa2 knock-down (KD) cells, PD cybrids and peripheral blood mononuclear cells (PBMC) from patients meeting the diagnostic criteria for PD. We quantified aSN aggregation, proteasome activity and protein ubiquitination levels. In PBMC of PD patient population we evaluated the aSN levels in the plasma and the influence of several demographic characteristics in the above mentioned determinations.
resultsWe found that ubiquitin-independent proteasome activity was up-regulated in SH-SY5Y ndufa2 KD cells while a downregulation was observed in PD cybrids and PBMC. Moreover, we observed an increase in protein ubiquitination that correlates with a decrease in ubiquitin-dependent proteasome activity. Accordingly, proteasome inhibition prevented ubiquitin-dependent aSN clearance. Ubiquitin-independent proteasome activity was positively correlated with ubiquitination in PBMC. We also report a negative correlation of chymotrypsin-like activity with age in control and late-onset PD groups. Total ubiquitin content is positively correlated with aSN oligomer levels, which leads to an age-dependent increase of aSN ubiquitination in LOPD. Moreover, aSN levels are increased in the plasma of PD patients.
interpretationaSN oligomers are ubiquitinated and we identified a ubiquitin-dependent clearance insufficiency with the accumulation of both aSN and ubiquitin. However, SH-SY5Y ndufa2 KD cells showed a significant up-regulation of ubiquitin-independent proteasomal enzymatic activity that could mean a cell rescue attempt. Moreover, we identified that UPS function is age-dependent in PBMC.
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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.