ArticleNature communications2023
Disrupting the α-synuclein-ESCRT interaction with a peptide inhibitor mitigates neurodegeneration in preclinical models of Parkinson's disease.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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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
32 citing papers in PubMed, 46 citations in OpenAlex.
- Sleep-circadian modulation of autophagy and glymphatic function: failure of coordinated brain clearance in Parkinson's disease.NPJ Parkinson's disease · 2026Review
- Cortical and basal ganglia beta oscillations and frequency-dependent DBS effects in the A53T Parkinson's disease rat model.NPJ Parkinson's disease · 2026Article
- Characterization of motor and non-motor features associated with bilateral nigral degeneration due to A53T alpha-synuclein in female rats.Scientific reports · 2026Article
- Facile Deep Brain Electrode Coating with MXene for Improved Electrode Performance.Advanced healthcare materials · 2026Article
- Modulating α-synuclein clearance: a comparison of high-frequency and direct current stimulation in preclinical models of Parkinson's disease.Brain communications · 2026Article
- A generative artificial intelligence approach for peptide antibiotic optimization.Nature machine intelligence · 2026Article
- Review
- Pathological α-synuclein perturbs nuclear integrity.Neurobiology of disease · 2025Article
- Deep learning reveals antibiotics in the archaeal proteome.Nature microbiology · 2025Article
- Alpha-synuclein modulates the positioning of endolysosomes in melanoma cells.Human molecular genetics · 2025Article
- Recent Advances in Autophagy and Immunotherapy for the Clearance of Aggregated α-Synuclein in Parkinson's Disease.Aging and disease · 2025Review
- Pathological α-synuclein elicits granulovacuolar degeneration independent of tau.Translational neurodegeneration · 2025Article
- Review
- Axonal transport of CHMP2b is regulated by kinesin-binding protein and disrupted by CHMP2bLife science alliance · 2025Article
- Listerin promotes α-synuclein degradation to alleviate Parkinson's disease through the ESCRT pathway.Science advances · 2025Article
- Generative latent diffusion language modeling yields anti-infective synthetic peptides.bioRxiv : the preprint server for biology · 2025Article
- Massively Parallel Screening of Toll/Interleukin-1 Receptor (TIR)-Derived Peptides Reveals Multiple Toll-Like Receptors (TLRs)-Targeting Immunomodulatory Peptides.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Studying the mechanisms of neurodegeneration:Frontiers in cellular neuroscience · 2025Review
- Pharmacological effects, molecular mechanisms and strategies to improve bioavailability of curcumin in the treatment of neurodegenerative diseases.Frontiers in pharmacology · 2025Review
- Nuclear pore dysfunction and disease: a complex opportunity.Nucleus (Austin, Tex.) · 2024Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
Accumulation of α-synuclein into toxic oligomers or fibrils is implicated in dopaminergic neurodegeneration in Parkinson's disease. Here we performed a high-throughput, proteome-wide peptide screen to identify protein-protein interaction inhibitors that reduce α-synuclein oligomer levels and their associated cytotoxicity. We find that the most potent peptide inhibitor disrupts the direct interaction between the C-terminal region of α-synuclein and CHarged Multivesicular body Protein 2B (CHMP2B), a component of the Endosomal Sorting Complex Required for Transport-III (ESCRT-III). We show that α-synuclein impedes endolysosomal activity via this interaction, thereby inhibiting its own degradation. Conversely, the peptide inhibitor restores endolysosomal function and thereby decreases α-synuclein levels in multiple models, including female and male human cells harboring disease-causing α-synuclein mutations. Furthermore, the peptide inhibitor protects dopaminergic neurons from α-synuclein-mediated degeneration in hermaphroditic C. elegans and preclinical Parkinson's disease models using female rats. Thus, the α-synuclein-CHMP2B interaction is a potential therapeutic target for neurodegenerative disorders.
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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.