ArticleNature structural & molecular biology2020
A short motif in the N-terminal region of α-synuclein is critical for both aggregation and function.
Article in Nature structural & molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed, 205 citations in OpenAlex.
- Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Condensate-driven triglyceride reduction links α-synuclein to mitochondrial dysfunction.EMBO reports · 2026Article
- Probing the Energy Landscape of α-Synuclein Amyloid Fibril Formation by Systematic K-to-Q Mutagenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Targeting soluble misfolded oligomers in anti-amyloid research.Nature reviews. Chemistry · 2026Review
- Development of an RNA aptamer as a therapeutic agent for synucleinopathies.Nature communications · 2026Article
- Temperature-Dependent Dynamics of Aβ42 and α-Synuclein Monomers and Early Oligomerization of Aβ42: Shared Residues Mediate Intra- and Intermolecular β-Sheets.ACS chemical neuroscience · 2026Article
- CPEB3 selectively inhibits α-synuclein aggregation without modulating TDP-43 pathology.FEBS letters · 2026Article
- Covalent Modulation of Protein Misfolding and Aggregation Processes in the Context of Neurodegenerative Diseases.Archiv der Pharmazie · 2026Review
- A Rigid Supramolecular Solution to a Flexible Problem: A Multifunctional Calix[4]arene-Based Strategy to Prevent α‑Synuclein Toxicity.ACS central science · 2026Article
- Reverse-engineering amyloid strains with generative protein design.bioRxiv : the preprint server for biology · 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
- Residue-Specific Modulation of Aggregation-Associated Interactions by Spermine in Tau, α‑Synuclein, and Aβ40.JACS Au · 2026Article
- Phosphatidylethanolamine modulates α-synuclein membrane-binding behavior.Biophysical journal · 2026Article
- Interactions Between Nutraceuticals and α-Synuclein Conformational States: Molecular Mechanisms and Neuroprotective Implications in Parkinson's Disease.International journal of molecular sciences · 2026Review
- Parkinson's disease-specific α-Synuclein variants potentially drive Lewy body formation by engaging in promiscuous and non-functional interactions.Communications biology · 2026Article
- Direct current stimulation induced reduction in α-synuclein in primary neurons: targeting Parkinson's disease.Brain communications · 2026Article
- Residue-Specific Modulation of Aggregation-Associated Interactions by Spermine in Tau, α-Synuclein, and Aβ40.bioRxiv : the preprint server for biology · 2025Article
- Energetic profiling reveals thermodynamic principles underlying amyloid fibril maturation.Nature communications · 2025Article
- Mapping the Role of Monomer Conformation in the Amyloid Formation of α-Synuclein Splice Variants.Journal of the American Chemical Society · 2025Article
54 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Aggregation of human α-synuclein (αSyn) is linked to Parkinson's disease (PD) pathology. The central region of the αSyn sequence contains the non-amyloid β-component (NAC) crucial for aggregation. However, how NAC flanking regions modulate αSyn aggregation remains unclear. Using bioinformatics, mutation and NMR, we identify a 7-residue sequence, named P1 (residues 36-42), that controls αSyn aggregation. Deletion or substitution of this 'master controller' prevents aggregation at pH 7.5 in vitro. At lower pH, P1 synergises with a sequence containing the preNAC region (P2, residues 45-57) to prevent aggregation. Deleting P1 (ΔP1) or both P1 and P2 (ΔΔ) also prevents age-dependent αSyn aggregation and toxicity in C. elegans models and prevents αSyn-mediated vesicle fusion by altering the conformational properties of the protein when lipid bound. The results highlight the importance of a master-controller sequence motif that controls both αSyn aggregation and function-a region that could be targeted to prevent aggregation in disease.
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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.