ArticleJournal of the American Chemical Society2024
Structure-Toxicity Relationship in Intermediate Fibrils from α-Synuclein Condensates.
Article in Journal of the American Chemical Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Cofactor-Free Tau Filaments Are Dynamic and Undergo Structural Evolution Driven by Thermodynamic Control.Journal of the American Chemical Society · 2026Article
- Sex-Specific Systemic Signatures in Parkinson's Disease: Integrated Biochemical and Metabolomic Evidence.Biomedicines · 2026Article
- α-Synuclein aggregation landscape from phase separation to neurotoxic intermediates.FEBS letters · 2026Review
- Fluorescent non-canonical amino acid as a site-specific conformational probe of prion formation.bioRxiv : the preprint server for biology · 2026Article
- Transient Interactions of α-Synuclein N- and C-Termini.ACS chemical neuroscience · 2026Article
- Nanoscale domains govern local diffusion and ageing within fused-in-sarcoma condensates.Nature nanotechnology · 2026Article
- Concentration-dependent mutational scanning probes the cellular folding landscape of α-synuclein in yeast.Protein science : a publication of the Protein Society · 2026Article
- Concentration-Dependent Mutational Scanning Probes the Cellular Folding Landscape of α-Synuclein in Yeast.bioRxiv : the preprint server for biology · 2025Article
- Surface wetting is a key determinant of α-synuclein condensate maturation.Communications chemistry · 2025Article
- Structural and cellular properties of human prion protein oligomers.Communications biology · 2025Article
- From Pathology to Materials Science and Engineering: Harnessing the Amyloid State for Biotechnological Applications.ACS applied materials & interfaces · 2025Review
- Structure and Dynamics of the Misfolding Intermediate in the Pathogenic T183A Prion Protein Mutant.Journal of chemical theory and computation · 2025Article
- Stimuli-Responsive Hydrogels from Liquid-Liquid Phase Separations of FUS-Derived Peptides.ACS applied materials & interfaces · 2025Article
- Alpha-synuclein fibril structures cluster into distinct classes.Biophysical journal · 2025Review
- The Structure of Human IAPP Fibrils Reflects Membrane and pH Conditions.Journal of the American Chemical Society · 2025Article
- Anionic Lipid Catalyzes the Generation of Cytotoxic Insulin Oligomers.Biomolecules · 2025Article
- Article
- Ligands for Protein Fibrils of Amyloid-β, α-Synuclein, and Tau.Chemical reviews · 2025Review
- Lipidic folding pathway of α-Synuclein via a toxic oligomer.Nature communications · 2025Article
- Inhibition of Phosphorylated Alpha-Synuclein Aggregation by Synthetic Protein Mimetics and Foldamers.ACS chemical neuroscience · 2025Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aberrant aggregation of α-synuclein (αS) into amyloid fibrils is associated with a range of highly debilitating neurodegenerative conditions, including Parkinson's disease. Although the structural properties of mature amyloids of αS are currently understood, the nature of transient protofilaments and fibrils that appear during αS aggregation remains elusive. Using solid-state nuclear magnetic resonance (ssNMR), cryogenic electron microscopy (cryo-EM), and biophysical methods, we here characterized intermediate amyloid fibrils of αS forming during the aggregation from liquid-like spherical condensates to mature amyloids adopting the structure of pathologically observed aggregates. These transient amyloid intermediates, which induce significant levels of cytotoxicity when incubated with neuronal cells, were found to be stabilized by a small core in an antiparallel β-sheet conformation, with a disordered N-terminal region of the protein remaining available to mediate membrane binding. In contrast, mature amyloids that subsequently appear during the aggregation showed different structural and biological properties, including low levels of cytotoxicity, a rearranged structured core embedding also the N-terminal region, and a reduced propensity to interact with the membrane. The characterization of these two fibrillar forms of αS, and the use of antibodies and designed mutants, enabled us to clarify the role of critical structural elements endowing intermediate amyloid species with the ability to interact with membranes and induce cytotoxicity.
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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.