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Amyloid β42 peptide is toxic to non-neural cells in Drosophila yielding a characteristic metabolite profile and the effect can be suppressed by PI3K

Arnés, Mercedes; Casas-Tintó, Sergio; Malmendal, Anders LU and Ferrús, Alberto (2017) In Biology Open 6(11). p.1664-1671
Abstract

The human Aβ42 peptide is associated with Alzheimer’s disease through its deleterious effects in neurons. Expressing the human peptide in adult Drosophila in a tissue- and time-controlled manner, we show that Aβ42 is also toxic in non-neural cells, neurosecretory and epithelial cell types in particular. This form of toxicity includes the aberrant signaling by Wingless morphogen leading to the eventual activation of Caspase 3. Preventing Caspase 3 activation by means of p53 keeps epithelial cells from elimination but maintains the Aβ42 toxicity yielding more severe deleterious effects to the organism. Metabolic profiling by nuclear magnetic resonance (NMR) of adult flies at selected ages post Aβ42 expression onset reveals characteristic... (More)

The human Aβ42 peptide is associated with Alzheimer’s disease through its deleterious effects in neurons. Expressing the human peptide in adult Drosophila in a tissue- and time-controlled manner, we show that Aβ42 is also toxic in non-neural cells, neurosecretory and epithelial cell types in particular. This form of toxicity includes the aberrant signaling by Wingless morphogen leading to the eventual activation of Caspase 3. Preventing Caspase 3 activation by means of p53 keeps epithelial cells from elimination but maintains the Aβ42 toxicity yielding more severe deleterious effects to the organism. Metabolic profiling by nuclear magnetic resonance (NMR) of adult flies at selected ages post Aβ42 expression onset reveals characteristic changes in metabolites as early markers of the pathological process. All morphological and most metabolic features of Aβ42 toxicity can be suppressed by the joint overexpression of PI3K.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amyloid β, Epithelial cells, Metabolomics, NMR, PI3K, Wingless
in
Biology Open
volume
6
issue
11
pages
8 pages
publisher
The Company of Biologists Ltd
external identifiers
  • scopus:85034258766
  • wos:000417557800008
ISSN
2046-6390
DOI
10.1242/bio.029991
language
English
LU publication?
yes
id
bfc6234d-1e94-4079-b7d6-a2dd1561e0ee
date added to LUP
2017-12-08 08:35:35
date last changed
2018-01-16 13:27:13
@article{bfc6234d-1e94-4079-b7d6-a2dd1561e0ee,
  abstract     = {<p>The human Aβ42 peptide is associated with Alzheimer’s disease through its deleterious effects in neurons. Expressing the human peptide in adult Drosophila in a tissue- and time-controlled manner, we show that Aβ42 is also toxic in non-neural cells, neurosecretory and epithelial cell types in particular. This form of toxicity includes the aberrant signaling by Wingless morphogen leading to the eventual activation of Caspase 3. Preventing Caspase 3 activation by means of p53 keeps epithelial cells from elimination but maintains the Aβ42 toxicity yielding more severe deleterious effects to the organism. Metabolic profiling by nuclear magnetic resonance (NMR) of adult flies at selected ages post Aβ42 expression onset reveals characteristic changes in metabolites as early markers of the pathological process. All morphological and most metabolic features of Aβ42 toxicity can be suppressed by the joint overexpression of PI3K.</p>},
  author       = {Arnés, Mercedes and Casas-Tintó, Sergio and Malmendal, Anders and Ferrús, Alberto},
  issn         = {2046-6390},
  keyword      = {Amyloid β,Epithelial cells,Metabolomics,NMR,PI3K,Wingless},
  language     = {eng},
  month        = {11},
  number       = {11},
  pages        = {1664--1671},
  publisher    = {The Company of Biologists Ltd},
  series       = {Biology Open},
  title        = {Amyloid β42 peptide is toxic to non-neural cells in Drosophila yielding a characteristic metabolite profile and the effect can be suppressed by PI3K},
  url          = {http://dx.doi.org/10.1242/bio.029991},
  volume       = {6},
  year         = {2017},
}