ArticleProceedings of the National Academy of Sciences of the United States of America2014
Solution conditions determine the relative importance of nucleation and growth processes in α-synuclein aggregation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 357 papers.
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Who cites it
357 citing papers in PubMed.
- Probing the Energy Landscape of α-Synuclein Amyloid Fibril Formation by Systematic K-to-Q Mutagenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- α-Synuclein Forms Distinct Micelle-Like Assemblies at Low Ionic Strengths.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cross-link Between CircRNAs and Neuroinflammation in Parkinson's Disease.Molecular neurobiology · 2026Review
- CPEB3 selectively inhibits α-synuclein aggregation without modulating TDP-43 pathology.FEBS letters · 2026Article
- α-Synuclein aggregation landscape from phase separation to neurotoxic intermediates.FEBS letters · 2026Review
- α-Synuclein overexpression increases the tropism of pre-formed fibrils and MSA-patient derived seeds towards oligodendroglia.Acta neuropathologica communications · 2026Article
- Fragmentation-Induced Disassembly and Reaggregation of α-Synuclein Amyloid Fibrils.ACS chemical neuroscience · 2026Article
- Cosolutes Modulate Polyubiquitin Fibrillation.ACS omega · 2026Article
- The amplification of α-synuclein amyloid fibrils.Biochemical Society transactions · 2026Review
- Transient Interactions of α-Synuclein N- and C-Termini.ACS chemical neuroscience · 2026Article
- Condensate State as Determinant of Amyloid Pathology in Neurodegeneration.Biomolecules · 2026Review
- Rapid elongation drives the exceptionally fast aggregation of the most common localized human amyloid medin.Communications chemistry · 2026Article
- WDR44 drives de novo α-synuclein aggregation at the lysosomal membrane and promotes neuronal dysfunction in Parkinson's Disease.bioRxiv : the preprint server for biology · 2026Article
- Article
- Modulation of α-Synuclein Oligomer and Aggregate Populations by pH and Metal Ions.Biomolecules · 2026Article
- Structural defects in amyloid-β fibrils drive secondary nucleation.Nature communications · 2026Article
- Concentration-dependent mutational scanning probes the cellular folding landscape of α-synuclein in yeast.Protein science : a publication of the Protein Society · 2026Article
- Parkinson's disease-specific α-Synuclein variants potentially drive Lewy body formation by engaging in promiscuous and non-functional interactions.Communications biology · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- STIP1/HOP promotes the formation of cytotoxic α-synuclein oligomers.Molecular neurodegeneration advances · 2026Article
297 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
The formation of amyloid fibrils by the intrinsically disordered protein α-synuclein is a hallmark of Parkinson disease. To characterize the microscopic steps in the mechanism of aggregation of this protein we have used in vitro aggregation assays in the presence of preformed seed fibrils to determine the molecular rate constant of fibril elongation under a range of different conditions. We show that α-synuclein amyloid fibrils grow by monomer and not oligomer addition and are subject to higher-order assembly processes that decrease their capacity to grow. We also find that at neutral pH under quiescent conditions homogeneous primary nucleation and secondary processes, such as fragmentation and surface-assisted nucleation, which can lead to proliferation of the total number of aggregates, are undetectable. At pH values below 6, however, the rate of secondary nucleation increases dramatically, leading to a completely different balance between the nucleation and growth of aggregates. Thus, at mildly acidic pH values, such as those, for example, that are present in some intracellular locations, including endosomes and lysosomes, multiplication of aggregates is much faster than at normal physiological pH values, largely as a consequence of much more rapid secondary nucleation. These findings provide new insights into possible mechanisms of α-synuclein aggregation and aggregate spreading in the context of Parkinson disease.
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