Abstract
ABSTRACTThe 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.
Highlights
Aβ42 is a proteolytic peptide from the amyloid precursor protein (APP), a ubiquitous transmembrane protein whose physiological function is still poorly characterized (Ludewig and Korte, 2016)
Since Alzheimer’s disease (AD) was first described as a neural disease, the vast majority of studies on Aβ42 have focused on neurons
Our study focuses on the muchneglected non-neuronal cell types as a strategy towards their potential use in early diagnosis of AD
Summary
Aβ42 is a proteolytic peptide from the amyloid precursor protein (APP), a ubiquitous transmembrane protein whose physiological function is still poorly characterized (Ludewig and Korte, 2016). The toxicity of Aβ42 in this non-neuronal cell type can be suppressed by PI3K. Taking advantage of this feature (Fig. S2), we searched for deleterious effects of Aβ42 in adult wings to determine if the toxicity in neurosecretory cells is evident in other cell types early in development.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
