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Increased Glucose Transport into Neurons Rescues A? Toxicity in Drosophila


Teresa Niccoli

Melissa Cabecinha

Anna Tillmann


Dalia Cardenes


Lucia Bettedi

Li Li


Jacqueline Dols

Linda Partridge


Glucose hypometabolism is a prominent feature of the brains of patients with Alzheimer's disease (AD). Disease progression is associated with a reduction in glucose transporters in both neurons and endothelial cells of the blood-brain barrier. However, whether increasing glucose transport into either of these cell types offers therapeutic potential remains unknown. Using an adult-onset Drosophila model of A? (amyloid beta) toxicity, we show that genetic overexpression of a glucose transporter, specifically in neurons, rescues lifespan, behavioral phenotypes, and neuronal morphology. This amelioration of A? toxicity is associated with a reduction in the protein levels of the unfolded protein response (UPR) negative master regulator Grp78 and an increase in the UPR. We further demonstrate that genetic downregulation of Grp78 activity also protects against A? toxicity, confirming a causal effect of its alteration on AD-related pathology. Metformin, a drug that stimulates glucose uptake in cells, mimicked these effects, with a concomitant reduction in Grp78 levels and rescue of the shortened lifespan and climbing defects of A?-expressing flies. Our findings demonstrate a protective effect of increased neuronal uptake of glucose against A? toxicity and highlight Grp78 as a novel therapeutic target for the treatment of AD.


Niccoli, T., Cabecinha, M., Tillmann, A., Kerr, F., Wong, C., Cardenes, D., …Partridge, L. (2016). Increased Glucose Transport into Neurons Rescues Aβ Toxicity in Drosophila. Current Biology, 26(17), 2291-2300.

Journal Article Type Article
Acceptance Date Jul 11, 2016
Online Publication Date Aug 11, 2016
Publication Date 2016-08
Deposit Date Aug 19, 2016
Publicly Available Date Aug 8, 2019
Journal Current Biology
Print ISSN 0960-9822
Electronic ISSN 1879-0445
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 26
Issue 17
Pages 2291-2300
Public URL


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