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A multi‐pathway perspective on protein aggregation: Implications for control of the rate and extent of amyloid formation
Author(s) -
Hall Damien,
Kardos József,
Edskes Herman,
Carver John A.,
Goto Yuji
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.01.032
Subject(s) - amyloid (mycology) , protein aggregation , chemistry , amyloid fibril , nucleation , amyloid disease , biophysics , kinetics , metastability , biochemistry , biology , amyloid β , disease , medicine , physics , organic chemistry , quantum mechanics , inorganic chemistry
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.