Identification of novel modifiers of Aβ toxicity by transcriptomic analysis in the fruitfly

Scientific Reports
G FavrinM E Giannakou

Abstract

The strongest risk factor for developing Alzheimer's Disease (AD) is age. Here, we study the relationship between ageing and AD using a systems biology approach that employs a Drosophila (fruitfly) model of AD in which the flies overexpress the human Aβ42 peptide. We identified 712 genes that are differentially expressed between control and Aβ-expressing flies. We further divided these genes according to how they change over the animal's lifetime and discovered that the AD-related gene expression signature is age-independent. We have identified a number of differentially expressed pathways that are likely to play an important role in the disease, including oxidative stress and innate immunity. In particular, we uncovered two new modifiers of the Aβ phenotype, namely Sod3 and PGRP-SC1b.

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Citations

Jun 23, 2015·Genesis : the Journal of Genetics and Development·Rachel LyneGos Micklem
Oct 24, 2014·Bioscience Reports·Michael J BlackneyJoel D Parker
Jun 5, 2020·Quarterly Reviews of Biophysics·Tessa SinnigeMichele Vendruscolo
Apr 20, 2018·The Journal of Cell Biology·Ying WangSiegfried Hekimi
Jul 14, 2020·Medicinal Research Reviews·Jiansong FangFeixiong Cheng
Feb 6, 2020·International Journal of Molecular Sciences·Youngjae JeonKyoung Sang Cho

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Datasets Mentioned

BETA
GPL14121
GSE48681

Methods Mentioned

BETA
transcription profiling
chips

Software Mentioned

R package Mfuzz
GraphPad Prism
R package
Limma
R mfuzz
maSigPro

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