ArticleProceedings of the National Academy of Sciences of the United States of America2023
Small molecules disaggregate alpha-synuclein and prevent seeding from patient brain-derived fibrils.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Beyond Amyloids: Neuroprotective Potential of Betanin and its Derivatives Against Alpha-Synuclein Aggregates and ROS Overload in Parkinson's Disease.Journal of molecular neuroscience : MN · 2026Article
- Machine learning-assisted screening of small-molecule drugs for suppressing protein aggregation and ROS generation based on ECL and CV dual-mode signals amplified by DNA.Chemical science · 2026Article
- Citric acid disassembles α-synuclein fibrils and reduces their cytotoxicity.Journal of pharmaceutical analysis · 2026Article
- Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Hydrophobic residues in the α-synuclein NAC domain drive seed-competent fibril formation and are targeted by peptide inhibitors.The FEBS journal · 2026Article
- Epigallocatechin-3-Gallate: A potential amyloid Fibril Disaggregator of Serum amyloid A1.Biochemistry and biophysics reports · 2025Article
- DDOX expands the repertoire of tetracyclines for Parkinson's disease by preventing the cellular uptake and intracellular impact of α-synuclein preformed fibrils.Scientific reports · 2025Article
- Identification of small molecule dimethyoxyphenyl piperazine inhibitors of alpha-synuclein fibril growth.Scientific reports · 2025Article
- Design of Ig-like binders targeting α-synuclein fibril for mitigating its pathological activities.Nature communications · 2025Article
- Article
- Protein aggregation and neurodegenerative disease: Structural outlook for the novel therapeutics.Proteins · 2025Review
- Structure-based discovery of forsythoside A as an effective inhibitor to reduce the neurotoxicity of amyloid β.Communications chemistry · 2025Article
- Liganded magnetic nanoparticles for magnetic resonance imaging of α-synuclein.NPJ Parkinson's disease · 2025Article
- Single-Molecule Insight Into α-Synuclein Fibril Structure and Mechanics Modulated by Chemical Compounds.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exploring the Potential of Biomimetic Peptides in Targeting Fibrillar and Filamentous Alpha-Synuclein-An In Silico and Experimental Approach to Parkinson's Disease.Biomimetics (Basel, Switzerland) · 2024Article
- Amyloid accelerator polyphosphate fits as the mystery density in α-synuclein fibrils.PLoS biology · 2024Article
- Review
- D-peptide-magnetic nanoparticles fragment tau fibrils and rescue behavioral deficits in a mouse model of Alzheimer's disease.Science advances · 2024Article
- Host-to-graft propagation of inoculated α-synuclein into transplanted human induced pluripotent stem cell-derived midbrain dopaminergic neurons.Regenerative therapy · 2024Article
- Ultrastructures of α-Synuclein Filaments in Synucleinopathy Brains and Experimental Models.Journal of movement disorders · 2024Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
The amyloid aggregation of alpha-synuclein within the brain is associated with the pathogenesis of Parkinson's disease (PD) and other related synucleinopathies, including multiple system atrophy (MSA). Alpha-synuclein aggregates are a major therapeutic target for treatment of these diseases. We identify two small molecules capable of disassembling preformed alpha-synuclein fibrils. The compounds, termed CNS-11 and CNS-11g, disaggregate recombinant alpha-synuclein fibrils in vitro, prevent the intracellular seeded aggregation of alpha-synuclein fibrils, and mitigate alpha-synuclein fibril cytotoxicity in neuronal cells. Furthermore, we demonstrate that both compounds disassemble fibrils extracted from MSA patient brains and prevent their intracellular seeding. They also reduce in vivo alpha-synuclein aggregates in
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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.