ArticleScience advances2023
Monitoring α-synuclein ubiquitination dynamics reveals key endosomal effectors mediating its trafficking and degradation.
Article in Science advances, 2023. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- α-Synuclein blocks endoplasmic reticulum co-translational protein translocation early in Parkinson's disease.Nature communications · 2026Article
- S-palmitoylation of the v-ATPase subunit RNAseK is necessary for Zika virus infection.Virology journal · 2026Article
- Synaptic vesicle architecture modulates α-synuclein conformation and pathogenic transitions in Parkinson's disease.Bioscience reports · 2026Review
- Alpha-Synuclein in Neurodegeneration: From Shared Biology to Disease-Specific Phenotypes.Cells · 2026Review
- Cross-Linking and Covalent Labeling Mass Spectrometry Reveal Proteoform-Driven Conformational Changes in Alpha Synuclein.Analytical chemistry · 2026Article
- When Proteins Go MAD-Misfolded, Amplified, Detected: Advances in α-Synuclein Pathophysiology and RT-QuIC Detection.Molecular neurobiology · 2026Review
- Breaking the proteasome balance: α-synuclein and the ubiquitin-proteasome system.Frontiers in cell and developmental biology · 2026Review
- Microautophagy: current understanding of its molecular mechanisms and functions.Autophagy reports · 2026Review
- Ubiquitin signatures on aggregating proteins in neurodegeneration.Essays in biochemistry · 2025Review
- Review
- Listerin promotes α-synuclein degradation to alleviate Parkinson's disease through the ESCRT pathway.Science advances · 2025Article
- OTUD5 Protects Dopaminergic Neurons by Promoting the Degradation of α-Synuclein in Parkinson's Disease Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Structures of Oligomeric States of Tau Protein, Amyloid-β, α-Synuclein and Prion Protein Implicated in Alzheimer's Disease, Parkinson's Disease and Prionopathies.International journal of molecular sciences · 2024Review
- Mono-UFMylation promotes misfolding-associated secretion of α-synuclein.Science advances · 2024Article
- Aquaporin-4 and Parkinson's Disease.International journal of molecular sciences · 2024Review
- Review
- ESCRT-III: a versatile membrane remodeling machinery and its implications in cellular processes and diseases.Animal cells and systems · 2024Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
While defective α-synuclein homeostasis is central to Parkinson's pathogenesis, fundamental questions about its degradation remain unresolved. We have developed a bimolecular fluorescence complementation assay in living cells to monitor de novo ubiquitination of α-synuclein and identified lysine residues 45, 58, and 60 as critical ubiquitination sites for its degradation. This is mediated by NBR1 binding and entry into endosomes in a process that involves ESCRT I-III for subsequent lysosomal degradation. Autophagy or the autophagic chaperone Hsc70 is dispensable for this pathway. Antibodies against diglycine-modified α-synuclein peptides confirmed that endogenous α-synuclein is similarly ubiquitinated in the brain and targeted to lysosomes in primary and iPSC-derived neurons. Ubiquitinated α-synuclein was detected in Lewy bodies and cellular models of aggregation, suggesting that it may be entrapped with endo/lysosomes in inclusions. Our data elucidate the intracellular trafficking of de novo ubiquitinated α-synuclein and provide tools for investigating the rapidly turned-over fraction of this disease-causing protein.
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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.