Related Experiment Video
Updated: May 21, 2026
12:58
Characterizing Individual Protein Aggregates by Infrared Nanospectroscopy and Atomic Force Microscopy
Published on: September 12, 2019
Fragmentation-Induced Disassembly and Reaggregation of α-Synuclein Amyloid Fibrils.
Fritjof Havemeister1, Vesa Halipi1, Marziyeh Ghaeidamini1
1Division of Chemical Biology, Department of Life Sciences, Chalmers University of Technology, Kemivägen 10, Gothenburg 412 96, Sweden.
ACS Chemical Neuroscience
|May 20, 2026
Summary
Parkinson's disease involves alpha-synuclein (α-syn) aggregation. This study reveals that fibril fragmentation accelerates α-syn structural changes, potentially linking to early-onset Parkinson's disease.
Area of Science:
- Biochemistry
- Neuroscience
- Protein Misfolding Diseases
Background:
- Alpha-synuclein (α-syn) aggregation is central to Parkinson's disease (PD) pathology.
- Kinetic studies have elucidated secondary nucleation and elongation in α-syn fibril growth.
- The role of fibril fragmentation in α-syn aggregation remains poorly understood.
Purpose of the Study:
- To investigate the impact of fibril fragmentation on α-syn aggregation kinetics and fibril properties.
- To explore the relationship between α-syn structural evolution, fibril stability, and Parkinson's disease onset.
Main Methods:
- A modified thioflavin-T (ThT) kinetic assay incorporating ultrasonication to induce fibril fragmentation.
- Monitoring of fibril fragmentation, dissociation, and regrowth kinetics using ThT fluorescence.
- Analysis of residual monomer concentration and comparison across different α-syn variants.
Main Results:
- Ultrasonication triggered α-syn fibril fragmentation, dissociation, and subsequent elongation-dominated regrowth.
- Specific early-onset PD-associated α-syn variants (A30P, E46K, A53T) showed increased ThT fluorescence upon regrowth, indicating structural changes.
- These variants exhibited higher residual monomer concentrations, suggesting altered monomer-fibril equilibria and decreased fibril stability compared to wild-type and H50Q variants.
Conclusions:
- Alpha-synuclein amyloid fibrils can undergo structural evolution that alters their ThT binding properties.
- Fibril fragmentation acts as a catalyst for these maturation processes.
- A potential link exists between the propensity for structural conversion, reduced fibril stability, and the early onset of Parkinson's disease.
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