ArticlePloS one2014
Targeting the intrinsically disordered structural ensemble of α-synuclein by small molecules as a potential therapeutic strategy for Parkinson's disease.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 71 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
71 citing papers in PubMed, 151 citations in OpenAlex.
- From synaptic development to degeneration: a narrative review of small molecule strategies targeting alpha-synuclein in Parkinson's disease.Metabolic brain disease · 2026Review
- Targeting the intrinsically disordered AR-NTD through a machine learning-based enhanced sampling workflow.Nature communications · 2026Article
- The intrinsically disordered protein SPE-56 is required for acrosomal-like exocytosis and fertility in Caenorhabditis elegans.Scientific reports · 2026Article
- Targeting protein disorder: the next hurdle in drug discovery.Nature reviews. Drug discovery · 2025Review
- IDRdecoder: a machine learning approach for rational drug discovery toward intrinsically disordered regions.Frontiers in bioinformatics · 2025Article
- Advances in Molecular Docking Techniques for Targeting Protein Misfolding in Neurodegenerative Diseases.Current pharmaceutical biotechnology · 2025Review
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- Unraveling the Behavior of Intrinsically Disordered Protein c-Myc: A Study Utilizing Gaussian-Accelerated Molecular Dynamics.ACS omega · 2024Article
- Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target.Viruses · 2023Review
- Parkinson's Disease: Exploring Different Animal Model Systems.International journal of molecular sciences · 2023Review
- Identification of Catechins' Binding Sites in Monomeric AInternational journal of molecular sciences · 2023Article
- Virtual Screening of Hepatitis B Virus Pre-Genomic RNA as a Novel Therapeutic Target.Molecules (Basel, Switzerland) · 2023Article
- Chemical tools for study and modulation of biomolecular phase transitions.Chemical science · 2022Review
- More is simpler: Decomposition of ligand-binding affinity for proteins being disordered.Protein science : a publication of the Protein Society · 2022Article
- A Small Molecule Stabilizes the Disordered Native State of the Alzheimer's Aβ Peptide.ACS chemical neuroscience · 2022Article
- Structure-Activity Relationships of Novel Tau Ligands: Passive Fibril Binders and Active Aggregation Inhibitors.ACS chemical biology · 2022Article
- Molecular Basis of Small-Molecule Binding to α-Synuclein.Journal of the American Chemical Society · 2022Article
- Small Molecule Sequestration of the Intrinsically Disordered Protein, p27Journal of molecular biology · 2021Article
- p27Cells · 2021Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
26 authors at 5 institutions in 3 countries.
Funding
Abstract
The misfolding of intrinsically disordered proteins such as α-synuclein, tau and the Aβ peptide has been associated with many highly debilitating neurodegenerative syndromes including Parkinson's and Alzheimer's diseases. Therapeutic targeting of the monomeric state of such intrinsically disordered proteins by small molecules has, however, been a major challenge because of their heterogeneous conformational properties. We show here that a combination of computational and experimental techniques has led to the identification of a drug-like phenyl-sulfonamide compound (ELN484228), that targets α-synuclein, a key protein in Parkinson's disease. We found that this compound has substantial biological activity in cellular models of α-synuclein-mediated dysfunction, including rescue of α-synuclein-induced disruption of vesicle trafficking and dopaminergic neuronal loss and neurite retraction most likely by reducing the amount of α-synuclein targeted to sites of vesicle mobilization such as the synapse in neurons or the site of bead engulfment in microglial cells. These results indicate that targeting α-synuclein by small molecules represents a promising approach to the development of therapeutic treatments of Parkinson's disease and related conditions.
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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.