ArticleRedox biology2021
Deficient immunoproteasome assembly drives gain of α-synuclein pathology in Parkinson's disease.
Article in Redox biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Astrocytic LMP2 Coordinates NF-κB and TGF-β1/Smad3 Signaling to Drive Neuroinflammation after Cerebral Ischemia/Reperfusion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The immunoproteasome as a neuroimmune hub in the central nervous system: from proteostasis stress to inflammatory pathology.Journal of neuroinflammation · 2026Review
- Current landscape of the immunoproteasome: implications for disease and therapy.Cell death discovery · 2025Review
- Article
- Microcystin-LR Exposure Damages Neurons by Inducing α-Syn Aggregation via MAPK4/GATA2/SNCA and PP2A/GRKs Pathways.Molecular neurobiology · 2025Article
- Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson's Disease with Potential Therapeutic Implications.Biomolecules · 2025Review
- Astrocyte-derived apolipoprotein D is required for neuronal survival in Parkinson's disease.NPJ Parkinson's disease · 2024Article
- Targeting Microglial Immunoproteasome: A Novel Approach in Neuroinflammatory-Related Disorders.ACS chemical neuroscience · 2024Review
- Interactions Between the Ubiquitin-Proteasome System, Nrf2, and the Cannabinoidome as Protective Strategies to Combat Neurodegeneration: Review on Experimental Evidence.Neurotoxicity research · 2024Review
- Using Redox Proteomics to Gain New Insights into Neurodegenerative Disease and Protein Modification.Antioxidants (Basel, Switzerland) · 2024Review
- Immunoproteasome acted as immunotherapy 'coffee companion' in advanced carcinoma therapy.Frontiers in immunology · 2024Review
- Quinpirole ameliorates nigral dopaminergic neuron damage in Parkinson's disease mouse model through activating GHS-R1a/DActa pharmacologica Sinica · 2023Article
- Deubiquitylase OTUD3 Mediates Endoplasmic Reticulum Stress through Regulating Fortilin Stability to Restrain Dopaminergic Neurons Apoptosis.Antioxidants (Basel, Switzerland) · 2023Article
- Liquid-Liquid Phase Separation Promotes Protein Aggregation and Its Implications in Ferroptosis in Parkinson's Disease Dementia.Oxidative medicine and cellular longevity · 2022Review
- Polo-Like Kinase 2: From Principle to Practice.Frontiers in oncology · 2022Review
- Adaptative Up-Regulation of PRX2 and PRX5 Expression Characterizes Brain from a Mouse Model of Chorea-Acanthocytosis.Antioxidants (Basel, Switzerland) · 2021Article
- Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant α-synuclein (α-Syn) accumulation resulting from proteasome dysfunction is considered as a prominent factor to initiate and aggravate the neurodegeneration in Parkinson's disease (PD). Although the involvement of 26S proteasome in proteostasis imbalance has been widely accepted, our knowledge about the regulation of immunoproteasome function and its potential role in α-Syn pathology remains limited. Immunoproteasome abundance and proteolytic activities depend on the finely tuned assembly process, especially β-ring formation mediated by the only well-known chaperone proteasome maturation protein (POMP). Here, we identified that α-Syn overexpression was associated with a reduction in immunoproteasome function, which in turn limited the degradation of polo-like kinase 2 (PLK2), exacerbated α-Syn Ser129 phosphorylation and aggregation, ultimately leading to the neurodegeneration. These effects could be dramatically attenuated by β5i overexpression. Mechanistically, α-Syn suppressed the transcriptional regulation of POMP by nuclear factor erythroid 2-related factor 2 (NRF2), thereby preventing the assembly of immunoproteasome β subunits. Dopaminergic neurons-specific overexpression of NRF2-POMP axis effectively rescued the aggregation of α-Syn and PD-like phenotypes. These findings characterized abnormal immunoproteasome assembly as a key contributor governing α-Syn accumulation and neurodegeneration, which might open up a new perspective for the implication of immunoproteasome in PD and provide approaches of manipulating immunoproteasome assembly for therapeutic purposes.
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