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

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 pa...

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Main Authors: Mercedes Arnés, Sergio Casas-Tintó, Anders Malmendal, Alberto Ferrús
Format: Article
Language:English
Published: The Company of Biologists 2017-11-01
Series:Biology Open
Subjects:
NMR
Online Access:http://bio.biologists.org/content/6/11/1664
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spelling doaj-15c2072a2e1c449883727e66688de9442021-06-02T15:44:08ZengThe Company of BiologistsBiology Open2046-63902017-11-016111664167110.1242/bio.029991029991Amyloid β42 peptide is toxic to non-neural cells in Drosophila yielding a characteristic metabolite profile and the effect can be suppressed by PI3KMercedes Arnés0Sergio Casas-Tintó1Anders Malmendal2Alberto Ferrús3 Dept. of Molecular, Cellular and Developmental Neurobiology, Instituto Cajal, Avda. Doctor Arce, 37, 28002 Madrid, Spain Dept. of Molecular, Cellular and Developmental Neurobiology, Instituto Cajal, Avda. Doctor Arce, 37, 28002 Madrid, Spain Biochemistry and Structural Biology, Center for Molecular Protein Science, Department of Chemistry, Lund University, P.O. Box 124, SE-22100 Lund, Sweden Dept. of Molecular, Cellular and Developmental Neurobiology, Instituto Cajal, Avda. Doctor Arce, 37, 28002 Madrid, Spain 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.http://bio.biologists.org/content/6/11/1664Amyloid βMetabolomicsNMRPI3KEpithelial cellsWingless
collection DOAJ
language English
format Article
sources DOAJ
author Mercedes Arnés
Sergio Casas-Tintó
Anders Malmendal
Alberto Ferrús
spellingShingle Mercedes Arnés
Sergio Casas-Tintó
Anders Malmendal
Alberto Ferrús
Amyloid β42 peptide is toxic to non-neural cells in Drosophila yielding a characteristic metabolite profile and the effect can be suppressed by PI3K
Biology Open
Amyloid β
Metabolomics
NMR
PI3K
Epithelial cells
Wingless
author_facet Mercedes Arnés
Sergio Casas-Tintó
Anders Malmendal
Alberto Ferrús
author_sort Mercedes Arnés
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
title_short Amyloid β42 peptide is toxic to non-neural cells in Drosophila yielding a characteristic metabolite profile and the effect can be suppressed by PI3K
title_full Amyloid β42 peptide is toxic to non-neural cells in Drosophila yielding a characteristic metabolite profile and the effect can be suppressed by PI3K
title_fullStr Amyloid β42 peptide is toxic to non-neural cells in Drosophila yielding a characteristic metabolite profile and the effect can be suppressed by PI3K
title_full_unstemmed Amyloid β42 peptide is toxic to non-neural cells in Drosophila yielding a characteristic metabolite profile and the effect can be suppressed by PI3K
title_sort amyloid β42 peptide is toxic to non-neural cells in drosophila yielding a characteristic metabolite profile and the effect can be suppressed by pi3k
publisher The Company of Biologists
series Biology Open
issn 2046-6390
publishDate 2017-11-01
description 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.
topic Amyloid β
Metabolomics
NMR
PI3K
Epithelial cells
Wingless
url http://bio.biologists.org/content/6/11/1664
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