Biophysical Reviews

, Volume 10, Issue 2, pp 493–502 | Cite as

Salt-induced formations of partially folded intermediates and amyloid fibrils suggests a common underlying mechanism

  • Yuji Goto
  • Masayuki Adachi
  • Hiroya Muta
  • Masatomo So


Amyloid fibrils are misfolded forms of proteins and are involved in various diseases. They have been studied extensively with the aim to obtain a comprehensive understanding of protein folding and misfolding and to use this knowledge to develop therapeutic strategies against the associated diseases. Salt conditions are important factors determining the formation and stability of amyloid fibrils. In the 1990s, salt effects were studied extensively to understand the conformational stability of acid-denatured proteins, and the results of these studies revealed the role of electrostatic repulsion in forming the compact intermediate states. In this review, we compare the effects of salts on the compact intermediate states with those on the formation of amyloid fibrils under acidic conditions. The results argue that both protein folding and misfolding are driven by the same forces, although the resultant conformations are distinct because they are monomeric and multimeric reactions, respectively.


Amyloid fibril Amorphous aggregation Molten globule Protein folding/misfolding Salt effects Supersaturation 



This work was supported by JSPS KAKENHI Grant Numbers 15H04362, 15 K14458, and 16H00836 and 17H06352, and by the SENTAN from Japan Agency for Medical Research and Development (AMED).

Compliance with ethical standards

Conflict of interest

Yuji Goto declares that he has no conflicts of interest. Masayuki Adachi declares that he has no conflicts of interest. Hiroya Muta declares that he has no conflicts of interest. Masatomo So declares that he has no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Institute for Protein ResearchOsaka UniversityOsakaJapan

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