Assessing the Causes and Consequences of Co-Polymerization in Amyloid Formation

Prion. Sep-Oct 2013;7(5):359-68. doi: 10.4161/pri.26415. Epub 2013 Sep 11.

Abstract

How, and why, different proteins form amyloid fibrils is most often studied in vitro using a single purified protein sequence. However, many amyloid diseases involve co-aggregation of different protein species, including proteins with/without post-translational modifications (e.g., different strains of PrP), proteins of different length (e.g., β₂-microglobulin and ΔN6, Aβ40, and Aβ42), sequence variants (e.g., Aβ and Aβ(ARC)), and proteins from different organisms (e.g., bovine PrP and human PrP). The consequences of co-aggregation of different proteins upon the structure, stability, species transmission and toxicity of the resulting amyloid aggregates is discussed here, including the role of co-aggregation in expanding the repertoire of oligomeric and fibrillar structures and how this can affect their biological and biophysical properties.

Keywords: amyloid; fibril; heteropolymers; polymorph; seeding; strain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Comment

MeSH terms

  • Amyloid / chemistry*
  • Humans
  • Mutant Proteins / chemistry*
  • Protein Precursors / chemistry*
  • beta 2-Microglobulin / chemistry*

Substances

  • Amyloid
  • Mutant Proteins
  • Protein Precursors
  • beta 2-Microglobulin