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

Hermansson, Erik; Schultz, Sebastian; Crowther, Damian; Linse, Sara LU ; Winblad, Bengt; Westermark, Gunilla; Johansson, Jan and Presto, Jenny (2014) In Disease Models and Mechanisms 7(6). p.659-665
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amyloid, Alzheimer's disease, Protein misfolding, Chaperone
in
Disease Models and Mechanisms
volume
7
issue
6
pages
659 - 665
publisher
The Company of Biologists Ltd
external identifiers
  • wos:000345002600007
  • scopus:84902267654
ISSN
1754-8411
DOI
10.1242/dmm.014787
language
English
LU publication?
yes
id
4e4e82e0-cfe3-4b40-9a8f-c0ab434af110 (old id 4985792)
date added to LUP
2015-01-26 13:48:01
date last changed
2017-10-29 03:23:28
@article{4e4e82e0-cfe3-4b40-9a8f-c0ab434af110,
  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.},
  author       = {Hermansson, Erik and Schultz, Sebastian and Crowther, Damian and Linse, Sara and Winblad, Bengt and Westermark, Gunilla and Johansson, Jan and Presto, Jenny},
  issn         = {1754-8411},
  keyword      = {Amyloid,Alzheimer's disease,Protein misfolding,Chaperone},
  language     = {eng},
  number       = {6},
  pages        = {659--665},
  publisher    = {The Company of Biologists Ltd},
  series       = {Disease Models and Mechanisms},
  title        = {The chaperone domain BRICHOS prevents CNS toxicity of amyloid-beta peptide in Drosophila melanogaster},
  url          = {http://dx.doi.org/10.1242/dmm.014787},
  volume       = {7},
  year         = {2014},
}