The small heat shock proteins αB-crystallin and Hsp27 suppress SOD1 aggregation in vitro

Cell Stress Chaperones. 2013 Mar;18(2):251-7. doi: 10.1007/s12192-012-0371-1. Epub 2012 Sep 21.

Abstract

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease. The mechanism that underlies amyotrophic lateral sclerosis (ALS) pathology remains unclear, but protein inclusions are associated with all forms of the disease. Apart from pathogenic proteins, such as TDP-43 and SOD1, other proteins are associated with ALS inclusions including small heat shock proteins. However, whether small heat shock proteins have a direct effect on SOD1 aggregation remains unknown. In this study, we have examined the ability of small heat shock proteins αB-crystallin and Hsp27 to inhibit the aggregation of SOD1 in vitro. We show that these chaperone proteins suppress the increase in thioflavin T fluorescence associated with SOD1 aggregation, primarily through inhibiting aggregate growth, not the lag phase in which nuclei are formed. αB-crystallin forms high molecular mass complexes with SOD1 and binds directly to SOD1 aggregates. Our data are consistent with an overload of proteostasis systems being associated with pathology in ALS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Benzothiazoles
  • HSP27 Heat-Shock Proteins / metabolism*
  • Humans
  • Spectrometry, Fluorescence
  • Superoxide Dismutase / chemistry
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Superoxide Dismutase-1
  • Thiazoles / chemistry
  • Thiazoles / metabolism
  • alpha-Crystallin B Chain / metabolism*

Substances

  • Benzothiazoles
  • HSP27 Heat-Shock Proteins
  • SOD1 protein, human
  • Thiazoles
  • alpha-Crystallin B Chain
  • thioflavin T
  • Superoxide Dismutase
  • Superoxide Dismutase-1