The chaperone domain BRICHOS prevents CNS toxicity of amyloid-beta peptide in Drosophila melanogaster

Research output: Contribution to journalArticle

Abstract

Aggregation of the amyloid-beta peptide (A beta) into toxic oligomers and amyloid fibrils is linked to the development of Alzheimer's disease (AD). Mutations of the BRICHOS chaperone domain are associated with amyloid disease and recent in vitro data show that BRICHOS efficiently delays A beta 42 oligomerization and fibril formation. We have generated transgenic Drosophila melanogaster flies that express the A beta 42 peptide and the BRICHOS domain in the central nervous system (CNS). Co-expression of A beta 42 and BRICHOS resulted in delayed A beta 42 aggregation and dramatic improvements of both lifespan and locomotor function compared with flies expressing A beta 42 alone. Moreover, BRICHOS increased the ratio of soluble: insoluble A beta 42 and bound to deposits of A beta 42 in the fly brain. Our results show that the BRICHOS domain efficiently reduces the neurotoxic effects of A beta 42, although significant A beta 42 aggregation is taking place. We propose that BRICHOS-based approaches should be explored with an aim towards the future prevention and treatment of AD.

Details

Authors
  • Erik Hermansson
  • Sebastian Schultz
  • Damian Crowther
  • Sara Linse
  • Bengt Winblad
  • Gunilla Westermark
  • Jan Johansson
  • Jenny Presto
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biological Sciences

Keywords

  • Amyloid, Alzheimer's disease, Protein misfolding, Chaperone
Original languageEnglish
Pages (from-to)659-665
JournalDisease Models and Mechanisms
Volume7
Issue number6
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes