Amyloid $42 peptide is toxic to non-neural cells in Drosophila yielding a characteristic metabolite profile and the effect can be suppressed by PI3K

M. Arnés, S. Casas-Tintó, A. Malmendal, A. Ferrús

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Resumé

textcopyright 2017, Company of Biologists Ltd. All rights reserved. The human A$42 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 A$42 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 A$42 toxicity yielding more severe deleterious effects to the organism. Metabolic profiling by nuclear magnetic resonance (NMR) of adult flies at selected ages post A$42 expression onset reveals characteristic changes in metabolites as early markers of the pathological process. All morphological and most metabolic features of A$42 toxicity can be suppressed by the joint overexpression of PI3K.
OriginalsprogEngelsk
TidsskriftBiology Open
Vol/bind6
Udgave nummer11
ISSN2046-6390
DOI
StatusUdgivet - 2017

Emneord

  • Amyloid $
  • Epithelial cells
  • Metabolomics
  • NMR
  • PI3K
  • Wingless

Citer dette

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title = "Amyloid $42 peptide is toxic to non-neural cells in Drosophila yielding a characteristic metabolite profile and the effect can be suppressed by PI3K",
abstract = "textcopyright 2017, Company of Biologists Ltd. All rights reserved. The human A$42 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 A$42 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 A$42 toxicity yielding more severe deleterious effects to the organism. Metabolic profiling by nuclear magnetic resonance (NMR) of adult flies at selected ages post A$42 expression onset reveals characteristic changes in metabolites as early markers of the pathological process. All morphological and most metabolic features of A$42 toxicity can be suppressed by the joint overexpression of PI3K.",
keywords = "Amyloid $, Epithelial cells, Metabolomics, NMR, PI3K, Wingless",
author = "M. Arn{\'e}s and S. Casas-Tint{\'o} and A. Malmendal and A. Ferr{\'u}s",
year = "2017",
doi = "10.1242/bio.029991",
language = "English",
volume = "6",
journal = "Biology Open",
issn = "2046-6390",
number = "11",

}

Amyloid $42 peptide is toxic to non-neural cells in Drosophila yielding a characteristic metabolite profile and the effect can be suppressed by PI3K. / Arnés, M.; Casas-Tintó, S.; Malmendal, A.; Ferrús, A.

I: Biology Open, Bind 6, Nr. 11, 2017.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Amyloid $42 peptide is toxic to non-neural cells in Drosophila yielding a characteristic metabolite profile and the effect can be suppressed by PI3K

AU - Arnés, M.

AU - Casas-Tintó, S.

AU - Malmendal, A.

AU - Ferrús, A.

PY - 2017

Y1 - 2017

N2 - textcopyright 2017, Company of Biologists Ltd. All rights reserved. The human A$42 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 A$42 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 A$42 toxicity yielding more severe deleterious effects to the organism. Metabolic profiling by nuclear magnetic resonance (NMR) of adult flies at selected ages post A$42 expression onset reveals characteristic changes in metabolites as early markers of the pathological process. All morphological and most metabolic features of A$42 toxicity can be suppressed by the joint overexpression of PI3K.

AB - textcopyright 2017, Company of Biologists Ltd. All rights reserved. The human A$42 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 A$42 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 A$42 toxicity yielding more severe deleterious effects to the organism. Metabolic profiling by nuclear magnetic resonance (NMR) of adult flies at selected ages post A$42 expression onset reveals characteristic changes in metabolites as early markers of the pathological process. All morphological and most metabolic features of A$42 toxicity can be suppressed by the joint overexpression of PI3K.

KW - Amyloid $

KW - Epithelial cells

KW - Metabolomics

KW - NMR

KW - PI3K

KW - Wingless

U2 - 10.1242/bio.029991

DO - 10.1242/bio.029991

M3 - Journal article

VL - 6

JO - Biology Open

JF - Biology Open

SN - 2046-6390

IS - 11

ER -