A multi-pathway perspective on protein aggregation: Implications for control of the rate and extent of amyloid formation

Damien Hall, J. Kardos, Herman Edskes, John A. Carver, Yuji Goto

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The nucleation-growth model has been used extensively for characterizing in vitro amyloid fibril formation kinetics and for simulating the relationship between amyloid and disease. In the majority of studies amyloid has been considered as the dominant, or sole, aggregation end product, with the presence of other competing non-amyloid aggregation processes, for example amorphous aggregate formation, being largely ignored. Here, we examine possible regulatory effects that off-pathway processes might exert on the rate and extent of amyloid formation - in particular their potential for providing false positives and negatives in the evaluation of anti-amyloidogenic agents. Furthermore, we investigate how such competing reactions might influence the standard interpretation of amyloid aggregation as a two-state system. We conclude by discussing our findings in terms of the general concepts of supersaturation and system metastability - providing some mechanistic insight as to how these empirical phenomena may manifest themselves in the amyloid arena.

Original languageEnglish
Pages (from-to)672-679
Number of pages8
JournalFEBS Letters
Volume589
Issue number6
DOIs
Publication statusPublished - Mar 12 2015

Fingerprint

Amyloid
Agglomeration
Proteins
Supersaturation
Nucleation
Kinetics
Growth

Keywords

  • Amorphous aggregation
  • Amyloid
  • Anti-amyloid ligand screen
  • Competition
  • Kinetic model
  • Regulation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

A multi-pathway perspective on protein aggregation : Implications for control of the rate and extent of amyloid formation. / Hall, Damien; Kardos, J.; Edskes, Herman; Carver, John A.; Goto, Yuji.

In: FEBS Letters, Vol. 589, No. 6, 12.03.2015, p. 672-679.

Research output: Contribution to journalArticle

Hall, Damien ; Kardos, J. ; Edskes, Herman ; Carver, John A. ; Goto, Yuji. / A multi-pathway perspective on protein aggregation : Implications for control of the rate and extent of amyloid formation. In: FEBS Letters. 2015 ; Vol. 589, No. 6. pp. 672-679.
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