BRICHOS binds to a designed amyloid-forming beta-protein and reduces proteasomal inhibition and aggresome formation

Abstract

The BRICHOS domain is associated with proliferative, degenerative and amyloid diseases, and it has been shown to inhibit fibril formation and toxicity of the Alzheimer's disease-associated amyloid beta-peptide. ProSP-C (prosurfactant protein C) BRICHOS binds to stretches of hydrophobic amino acid residues, which are unfolded or in beta-strand conformation, suggesting that it may have broad anti-amyloid activity. We have studied the effect of the proSP-C BRICHOS domain on the designed amyloidogenic beta-sheet proteins beta 17 and beta 23. beta 17 expressed in the secretory pathway of HEK (human embryonic kidney)-293 cells forms intracellular inclusions, whereas beta 23 is rapidly degraded. Co-expression of BRICHOS leads to a reduction in beta 17 inclusion size and increased levels of soluble beta 17 and beta 23. Furthermore, BRICHOS interacts with the beta-proteins intracellularly, reduces their ubiquitination and decreases aggresome formation and proteasomal inhibition. Collectively, these data suggest that BRICHOS is capable of delaying the aggregation process and toxicity of amyloidogenic proteins in a generic manner.

Keywords

Alzheimer's disease; amyloid; BRICHOS; molecular chaperone; protein conformation; protein inclusions

Published in

Biochemical Journal
2016, Volume: 473, number: 2, pages: 167-178 Publisher: PORTLAND PRESS LTD

SLU Authors

• Johansson, Jan

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    
  • Karolinska Institute
  • Tallinn University

UKÄ Subject classification

Neurosciences
Biochemistry and Molecular Biology


Publication identifier

DOI: https://doi.org/10.1042/BJ20150920

Permanent link to this page (URI)

https://res.slu.se/id/publ/83106