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The chaperone domain BRICHOS prevents CNS toxicity of amyloid-β peptide in Drosophila melanogaster
Aggregation of the amyloid-β peptide (Aβ) 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 Aβ42 oligomerizatio...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Limited
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036473/ https://www.ncbi.nlm.nih.gov/pubmed/24682783 http://dx.doi.org/10.1242/dmm.014787 |
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author | Hermansson, Erik Schultz, Sebastian Crowther, Damian Linse, Sara Winblad, Bengt Westermark, Gunilla Johansson, Jan Presto, Jenny |
author_facet | Hermansson, Erik Schultz, Sebastian Crowther, Damian Linse, Sara Winblad, Bengt Westermark, Gunilla Johansson, Jan Presto, Jenny |
author_sort | Hermansson, Erik |
collection | PubMed |
description | Aggregation of the amyloid-β peptide (Aβ) 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 Aβ42 oligomerization and fibril formation. We have generated transgenic Drosophila melanogaster flies that express the Aβ42 peptide and the BRICHOS domain in the central nervous system (CNS). Co-expression of Aβ42 and BRICHOS resulted in delayed Aβ42 aggregation and dramatic improvements of both lifespan and locomotor function compared with flies expressing Aβ42 alone. Moreover, BRICHOS increased the ratio of soluble:insoluble Aβ42 and bound to deposits of Aβ42 in the fly brain. Our results show that the BRICHOS domain efficiently reduces the neurotoxic effects of Aβ42, although significant Aβ42 aggregation is taking place. We propose that BRICHOS-based approaches should be explored with an aim towards the future prevention and treatment of AD. |
format | Online Article Text |
id | pubmed-4036473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Company of Biologists Limited |
record_format | MEDLINE/PubMed |
spelling | pubmed-40364732014-07-03 The chaperone domain BRICHOS prevents CNS toxicity of amyloid-β peptide in Drosophila melanogaster Hermansson, Erik Schultz, Sebastian Crowther, Damian Linse, Sara Winblad, Bengt Westermark, Gunilla Johansson, Jan Presto, Jenny Dis Model Mech Research Article Aggregation of the amyloid-β peptide (Aβ) 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 Aβ42 oligomerization and fibril formation. We have generated transgenic Drosophila melanogaster flies that express the Aβ42 peptide and the BRICHOS domain in the central nervous system (CNS). Co-expression of Aβ42 and BRICHOS resulted in delayed Aβ42 aggregation and dramatic improvements of both lifespan and locomotor function compared with flies expressing Aβ42 alone. Moreover, BRICHOS increased the ratio of soluble:insoluble Aβ42 and bound to deposits of Aβ42 in the fly brain. Our results show that the BRICHOS domain efficiently reduces the neurotoxic effects of Aβ42, although significant Aβ42 aggregation is taking place. We propose that BRICHOS-based approaches should be explored with an aim towards the future prevention and treatment of AD. The Company of Biologists Limited 2014-06 2014-03-28 /pmc/articles/PMC4036473/ /pubmed/24682783 http://dx.doi.org/10.1242/dmm.014787 Text en © 2014. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Hermansson, Erik Schultz, Sebastian Crowther, Damian Linse, Sara Winblad, Bengt Westermark, Gunilla Johansson, Jan Presto, Jenny The chaperone domain BRICHOS prevents CNS toxicity of amyloid-β peptide in Drosophila melanogaster |
title | The chaperone domain BRICHOS prevents CNS toxicity of amyloid-β peptide in Drosophila melanogaster |
title_full | The chaperone domain BRICHOS prevents CNS toxicity of amyloid-β peptide in Drosophila melanogaster |
title_fullStr | The chaperone domain BRICHOS prevents CNS toxicity of amyloid-β peptide in Drosophila melanogaster |
title_full_unstemmed | The chaperone domain BRICHOS prevents CNS toxicity of amyloid-β peptide in Drosophila melanogaster |
title_short | The chaperone domain BRICHOS prevents CNS toxicity of amyloid-β peptide in Drosophila melanogaster |
title_sort | chaperone domain brichos prevents cns toxicity of amyloid-β peptide in drosophila melanogaster |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036473/ https://www.ncbi.nlm.nih.gov/pubmed/24682783 http://dx.doi.org/10.1242/dmm.014787 |
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