Kinetic diversity of amyloid oligomers

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Abstract
Significance: Protein oligomers are a fundamental component of amyloidogenic disorders such as Alzheimer’s disease, being both critical intermediates in the formation of amyloid fibrils and the most toxic species on the protein aggregation pathway. Here, we derive general analytical expressions for the chemical kinetics of the oligomers generated during amyloid-formation reactions and explain how these may be used to categorize oligomers according to their basic physicochemical properties. By applying this framework to experimental kinetic data on the aggregation of a wide range of amyloidogenic proteins, we are able to determine features common to all amyloid oligomers. In particular, most are not capable of rapid growth by monomer addition, and most dissociate rather than mature into fibrils.
Funding Information
  • National Natural Science Foundation of China (21673278)
  • National Natural Science Foundation of China (31920103011)

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