Oncotarget

Research Papers: Gerotarget (Focus on Aging):

GULP1/CED-6 ameliorates amyloid-β toxicity in a Drosophila model of Alzheimer’s disease

Wai Yin Vivien Chiu, Alex Chun Koon, Jacky Chi Ki Ngo, Ho Yin Edwin Chan and Kwok-Fai Lau _

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Oncotarget. 2017; 8:99274-99283. https://doi.org/10.18632/oncotarget.20062

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Abstract

Wai Yin Vivien Chiu1,*, Alex Chun Koon1,*, Jacky Chi Ki Ngo1, Ho Yin Edwin Chan1 and Kwok-Fai Lau1

1 School of Life Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR

* These authors have contributed equally to this work

Correspondence to:

Kwok-Fai Lau, email:

Keywords: CED-6, APP, Aβ, neurodegeneration, neurotoxicity, Gerotarget

Received: June 13, 2017 Accepted: July 30, 2017 Published: August 08, 2017

Abstract

Amyloidogenic processing of APP by β- and γ-secretases leads to the generation of amyloid-β peptide (Aβ), and the accumulation of Aβ in senile plaques is a hallmark of Alzheimer’s disease (AD). Understanding the mechanisms of APP processing is therefore paramount. Increasing evidence suggests that APP intracellular domain (AICD) interacting proteins influence APP processing. In this study, we characterized the overexpression of AICDinteractor GULP1 in a Drosophila AD model expressing human BACE and APP695. Transgenic GULP1 significantly lowered the levels of both Aβ1-40 and Aβ1-42 without decreasing the BACE and APP695 levels. Overexpression of GULP1 also reduced APP/BACE-mediated retinal degeneration, rescued motor dysfunction and extended longevity of the flies. Our results indicate that GULP1 regulate APP processing and reduce neurotoxicity in a Drosophila AD model.


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