Solution conditions determine the relative importance of nucleation and growth processes in α-synuclein aggregation
University of Cambridge · Physical Sciences (United States) · +1 more institution
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…
Citation impact
- FWCI
- 25.98
- Percentile
- 100%
- References
- 53
Authors
8Topics & keywords
- Nucleation
- Fibril
- Biophysics
- Chemistry
- Protein aggregation
- Context (archaeology)
- Amyloid (mycology)
- Proteostasis
- Life in Land