ArticleNature communications2022
Single residue modulators of amyloid formation in the N-terminal P1-region of α-synuclein.
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 31 papers.
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Who cites it
31 citing papers in PubMed, 54 citations in OpenAlex.
- CPEB3 selectively inhibits α-synuclein aggregation without modulating TDP-43 pathology.FEBS letters · 2026Article
- Nanopipettes Enable Native Mass Spectrometry Studies of the Intrinsically Disordered Protein α-Synuclein in Biochemical Buffers.Analytical chemistry · 2026Article
- In silico peptide self-assembly reveals the importance of N-terminal motifs and the inhibition mechanism of the mutation L38M in α-synuclein fibrillation.Protein science : a publication of the Protein Society · 2026Article
- Hydrophobic residues in the α-synuclein NAC domain drive seed-competent fibril formation and are targeted by peptide inhibitors.The FEBS journal · 2026Article
- Mapping the Role of Monomer Conformation in the Amyloid Formation of α-Synuclein Splice Variants.Journal of the American Chemical Society · 2025Article
- Dissecting the Molecular Determinants of α-synuclein Phase Separation and Condensate Aging: The Pivotal Role of β-Sheet-Rich Motifs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Protein Recognition of Linear and Cyclic Peptides of Homologous Sequences Implicated in the Aggregation of α-Synuclein.The journal of physical chemistry. B · 2025Article
- ZnJournal of the American Chemical Society · 2025Article
- Is synuclein aggregation a derived or ancestral trait? Ancestral sequence reconstruction uncovers stepwise evolution of synuclein aggregation.bioRxiv : the preprint server for biology · 2025Article
- Defining essential charged residues in fibril formation of a lysosomal derived N-terminal α-synuclein truncation.Nature communications · 2025Article
- Molecular Rotors Detect the Formation and Conversion of α-Synuclein Oligomers.ACS applied materials & interfaces · 2025Article
- Design and Development of Natural-Product-Derived Nanoassemblies and Their Interactions with Alpha Synuclein.Biomimetics (Basel, Switzerland) · 2025Article
- Structures of Oligomeric States of Tau Protein, Amyloid-β, α-Synuclein and Prion Protein Implicated in Alzheimer's Disease, Parkinson's Disease and Prionopathies.International journal of molecular sciences · 2024Review
- Exploring the Impact of Physiological C-Terminal Truncation on α-Synuclein Conformations to Unveil Mechanisms Regulating Pathological Aggregation.Journal of chemical information and modeling · 2024Article
- Residues 2 to 7 of α-synuclein regulate amyloid formation via lipid-dependent and lipid-independent pathways.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Potent Sybody Selectively Inhibits α-Synuclein Amyloid Formation by Binding to the P1 Region.Journal of medicinal chemistry · 2024Article
- Current trends in basic research on Parkinson's disease: from mitochondria, lysosome to α-synuclein.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Structural Insights into Seeding Mechanisms of hIAPP Fibril Formation.Journal of the American Chemical Society · 2024Article
- A Targetable N-Terminal Motif Orchestrates α-Synuclein Oligomer-to-Fibril Conversion.Journal of the American Chemical Society · 2024Article
- Interplay of α-synuclein with Lipid Membranes: Cooperative Adsorption, Membrane Remodeling and Coaggregation.JACS Au · 2024Review
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Alpha-synuclein (αSyn) is a protein involved in neurodegenerative disorders including Parkinson's disease. Amyloid formation of αSyn can be modulated by the 'P1 region' (residues 36-42). Here, mutational studies of P1 reveal that Y39A and S42A extend the lag-phase of αSyn amyloid formation in vitro and rescue amyloid-associated cytotoxicity in C. elegans. Additionally, L38I αSyn forms amyloid fibrils more rapidly than WT, L38A has no effect, but L38M does not form amyloid fibrils in vitro and protects from proteotoxicity. Swapping the sequence of the two residues that differ in the P1 region of the paralogue γSyn to those of αSyn did not enhance fibril formation for γSyn. Peptide binding experiments using NMR showed that P1 synergises with residues in the NAC and C-terminal regions to initiate aggregation. The remarkable specificity of the interactions that control αSyn amyloid formation, identifies this region as a potential target for therapeutics, despite their weak and transient nature.
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