ArticleNature communications2022
Heparin induces α-synuclein to form new fibril polymorphs with attenuated neuropathology.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 63 citations in OpenAlex.
- A functional amyloid scaffold shapes insect egg coats.bioRxiv : the preprint server for biology · 2026Article
- Amyloid fibril polymorphism: Structural mechanisms of assembly and the links to disease.Current opinion in structural biology · 2026Review
- Modulation of biomolecular condensation of alpha-synuclein variants by eprodisate.Communications chemistry · 2026Article
- Lipid Acyl Chain-Driven α-Synuclein Fibril Polymorphisms and Neuronal Pathologies.ACS chemical neuroscience · 2026Article
- Differences in α-synuclein conformational states in physiologically relevant pH/NaThe Analyst · 2026Article
- Structural and mechanistic characterization of heparin interactions with tau fibrils.The Journal of biological chemistry · 2026Article
- Formation of Condition-Dependent Alpha-Synuclein Fibril Strain in Artificial Cerebrospinal Fluid.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spontaneous generation of diverse recombinant prion strains: sulfated glycan cofactors facilitate strain emergence but do not determine specific strain properties.Acta neuropathologica communications · 2025Article
- Alpha-synuclein fibril structures cluster into distinct classes.Biophysical journal · 2025Review
- Chronic sleep deprivation induces plasma exosome-derived miR-150-5p downregulation as a novel mechanism involved in Parkinson's disease progression by targeting DCLK1.Journal of translational medicine · 2025Article
- Conformational Switch in the Alpha-Synuclein C-Terminal Domain Directs Its Fibril Polymorphs.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Effect of RNA on the supramolecular architecture of α-synuclein fibrils.Biophysical journal · 2025Article
- Ligands for Protein Fibrils of Amyloid-β, α-Synuclein, and Tau.Chemical reviews · 2025Review
- Amyloid-forming property of the N-terminal 1-70 residues of human apolipoprotein A-IV.Scientific reports · 2025Article
- Serum Amyloid A Binding to Glycosaminoglycans is Synergistic with Amyloid Formation: Therapeutic Targeting in the Inflammation-linked Amyloidosis.Journal of molecular biology · 2025Article
- Elucidating the Mechanism of Recognition and Binding of Heparin to Amyloid Fibrils of Serum Amyloid A.Biochemistry · 2025Article
- Solid-state NMR assignment of α-synuclein polymorph prepared from helical intermediate.Biomolecular NMR assignments · 2024Article
- In Vitro Cell Model Investigation of Alpha-Synuclein Aggregate Morphology Using Spectroscopic Imaging.International journal of molecular sciences · 2024Article
- Mouse α-synuclein fibrils are structurally and functionally distinct from human fibrils associated with Lewy body diseases.Science advances · 2024Article
- Inhibitor Development for α-Synuclein Fibril's Disordered Region to Alleviate Parkinson's Disease Pathology.Journal of the American Chemical Society · 2024Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
α-Synuclein (α-syn), as a primary pathogenic protein in Parkinson's disease (PD) and other synucleinopathies, exhibits a high potential to form polymorphic fibrils. Chemical ligands have been found to involve in the assembly of α-syn fibrils in patients' brains. However, how ligands influence the fibril polymorphism remains vague. Here, we report the near-atomic structures of α-syn fibrils in complex with heparin, a representative glycosaminoglycan (GAG), determined by cryo-electron microscopy (cryo-EM). The structures demonstrate that the presence of heparin completely alters the fibril assembly via rearranging the charge interactions of α-syn both at the intramolecular and the inter-protofilamental levels, which leads to the generation of four fibril polymorphs. Remarkably, in one of the fibril polymorphs, α-syn folds into a distinctive conformation that has not been observed previously. Moreover, the heparin-α-syn complex fibrils exhibit diminished neuropathology in primary neurons. Our work provides the structural mechanism for how heparin determines the assembly of α-syn fibrils, and emphasizes the important role of biological polymers in the conformational selection and neuropathology regulation of amyloid fibrils.
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