ArticleScientific reports2022
Mechanisms of enhanced aggregation and fibril formation of Parkinson's disease-related variants of α-synuclein.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 78 citations in OpenAlex.
- Probing the Energy Landscape of α-Synuclein Amyloid Fibril Formation by Systematic K-to-Q Mutagenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Fragmentation-Induced Disassembly and Reaggregation of α-Synuclein Amyloid Fibrils.ACS chemical neuroscience · 2026Article
- Mechanism-selective inhibition of α-synuclein aggregation by the chaperone-like BRICHOS domain.The Journal of biological chemistry · 2026Article
- Human and Mouse Alpha-Synuclein Fibrillation: Impact on h-FTAA Binding and Advancing Strain-Specific Biomarkers in PD Animal Models.International journal of molecular sciences · 2026Article
- Differences in α-synuclein conformational states in physiologically relevant pH/NaThe Analyst · 2026Article
- The Progress of Active Immunotherapy for Parkinson's Disease.International journal of molecular sciences · 2026Review
- Antiviral innate immunity induces alpha synuclein phosphorylation at serine129 in neurons independent of aggregation.NPJ Parkinson's disease · 2026Article
- Phosphatidylethanolamine modulates α-synuclein membrane-binding behavior.Biophysical journal · 2026Article
- Heat shock protein 10 as a chaperone modulating α-synuclein amyloid fibril formation.Protein science : a publication of the Protein Society · 2026Article
- Interactions Between Nutraceuticals and α-Synuclein Conformational States: Molecular Mechanisms and Neuroprotective Implications in Parkinson's Disease.International journal of molecular sciences · 2026Review
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Co-Expression of Mutant Tau and α-Synuclein in Neurons Promotes Tau Phosphorylation, Neuronal Loss, and Neuroinflammation in Mouse Brain.Molecular neurobiology · 2025Article
- Article
- Is synuclein aggregation a derived or ancestral trait? Ancestral sequence reconstruction uncovers stepwise evolution of synuclein aggregation.bioRxiv : the preprint server for biology · 2025Article
- Evaluating alpha-synuclein proteinopathy and consequences for birdsong in zebra finch basal ganglia area X.Behavioural brain research · 2025Article
- Novel in situ seeding immunodetection assay uncovers neuronal-driven alpha-synuclein seeding in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Lipid packing defects are necessary and sufficient for membrane binding of α-synuclein.Communications biology · 2025Article
- Photochemically synthesized gold nanoparticles conjugated with Boswellic acid inhibit alpha synuclein aggregation and delay fibrillation kinetics.Scientific reports · 2025Article
- Lipid Packing Defects are Necessary and Sufficient for Membrane Binding of α-Synuclein.bioRxiv : the preprint server for biology · 2025Article
- Effect of hydrogen sulfide on alpha-synuclein aggregation and cell viability.Scientific reports · 2025Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aggregation of α-synuclein (α-syn) into amyloid fibrils is closely associated with Parkinson's disease (PD). Familial mutations or posttranslational truncations in α-syn are known as risk factor for PD. Here, we examined the effects of the PD-related A30P or A53T point mutation and C-terminal 123-140 or 104-140 truncation on the aggregating property of α-syn based on the kinetic and thermodynamic analyses. Thioflavin T fluorescence measurements indicated that A53T, Δ123‒140, and Δ104-140 variants aggregated faster than WT α-syn, in which the A53T mutation markedly increases nucleation rate whereas the Δ123‒140 or Δ104‒140 truncation significantly increases both nucleation and fibril elongation rates. Ultracentrifugation and western blotting analyses demonstrated that these mutations or truncations promote the conversion of monomer to aggregated forms of α-syn. Analysis of the dependence of aggregation reaction of α-syn variants on the monomer concentration suggested that the A53T mutation enhances conversion of monomers to amyloid nuclei whereas the C-terminal truncations, especially the Δ104-140, enhance autocatalytic aggregation on existing fibrils. In addition, thermodynamic analysis of the kinetics of nucleation and fibril elongation of α-syn variants indicated that both nucleation and fibril elongation of WT α-syn are enthalpically and entropically unfavorable. Interestingly, the unfavorable activation enthalpy of nucleation greatly decreases for the A53T and becomes reversed in sign for the C-terminally truncated variants. Taken together, our results indicate that the A53T mutation and the C-terminal truncation enhance α-syn aggregation by reducing unfavorable activation enthalpy of nucleation, and the C-terminal truncation further triggers the autocatalytic fibril elongation on the fibril surfaces.
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