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Portrait of Sara Snogerup Linse

Sara Linse


Portrait of Sara Snogerup Linse

Surface-Catalyzed Secondary Nucleation Dominates the Generation of Toxic IAPP Aggregates


  • Diana C. Rodriguez Camargo
  • Sean Chia
  • Joseph Menzies
  • Benedetta Mannini
  • Georg Meisl
  • Martin Lundqvist
  • Christin Pohl
  • Katja Bernfur
  • Veronica Lattanzi
  • Johnny Habchi
  • Samuel I.A. Cohen
  • Tuomas P.J. Knowles
  • Michele Vendruscolo
  • Sara Linse

Summary, in English

The aggregation of the human islet amyloid polypeptide (IAPP) is associated with diabetes type II. A quantitative understanding of this connection at the molecular level requires that the aggregation mechanism of IAPP is resolved in terms of the underlying microscopic steps. Here we have systematically studied recombinant IAPP, with amidated C-terminus in oxidised form with a disulphide bond between residues 3 and 7, using thioflavin T fluorescence to monitor the formation of amyloid fibrils as a function of time and IAPP concentration. We used global kinetic analyses to connect the macroscopic measurements of aggregation to the microscopic mechanisms, and show that the generation of new aggregates is dominated by the secondary nucleation of monomers on the fibril surface. We then exposed insulinoma cells to aliquots extracted from different time points of the aggregation process, finding the highest toxicity at the midpoint of the reaction, when the secondary nucleation rate reaches its maximum. These results identify IAPP oligomers as the most cytotoxic species generated during IAPP aggregation, and suggest that compounds that target secondary nucleation of IAPP could be most effective as therapeutic candidates for diabetes type II.


  • Biochemistry and Structural Biology
  • NanoLund: Center for Nanoscience
  • MultiPark: Multidisciplinary research focused on Parkinson´s disease

Publishing year





Frontiers in Molecular Biosciences



Document type

Journal article


Frontiers Media S. A.


  • Biochemistry and Molecular Biology


  • amyloid formation
  • optical spectroscopy
  • peptide purification
  • reaction mechanism
  • self-assembly




  • ISSN: 2296-889X