title: Evaluating nuclei concentration in amyloid fibrillation reactions using back-calculation approach.
abstract: BACKGROUND
  In spite of our extensive knowledge of the more than 20 proteins associated with different amyloid diseases, we do not know how amyloid toxicity occurs or how to block its action. Recent contradictory reports suggest that the fibrils and/or the oligomer precursors cause toxicity. An estimate of their temporal concentration may broaden understanding of the amyloid aggregation process.
  
  
  RESULTS
  Assuming that conversion of folded protein to fibril is initiated by a nucleation event, we back-calculate the distribution of nuclei concentration. The temporal in vitro concentration of nuclei for the model hormone, recombinant human insulin, is estimated to be in the picomolar range. This is a conservative estimate since the back-calculation method is likely to overestimate the nuclei concentration because it does not take into consideration fibril fragmentation, which would lower the amount of nuclei
  
  
  CONCLUSIONS
  Because of their propensity to form aggregates (non-ordered) and fibrils (ordered), this very low concentration could explain the difficulty in isolating and blocking oligomers or nuclei toxicity and the long onset time for amyloid diseases.
authors.affiliation: Howard P. Isermann Department of Chemical and Biological Engineering and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, United States of America.
authors.forename: Mirco
authors.initials: M
authors.lastname: Sorci
authors.forename: Whitney
authors.initials: W
authors.lastname: Silkworth
authors.forename: Timothy
authors.initials: T
authors.lastname: Gehan
authors.forename: Georges
authors.initials: G
authors.lastname: Belfort
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D000682:Amyloid; D007328:Insulin; D011994:Recombinant Proteins