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Increased Glucose Transport into Neurons Rescues Aβ Toxicity in Drosophila
Niccoli T, Cabecinha M, Tillmann A, Kerr F, Wong CT, Cardenes D, Vincent AJ, Bettedi L et al.. Current biology : CB, 2016-08-11
Topic: Brain proteins, microglia and lab models
Plain-language summary
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 Aβ (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 Aβ 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 Aβ 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 Aβ-expressing flies. Our findings demonstrate a protective effect of increased neuronal uptake of glucose against Aβ toxicity and highlight Grp78 as a novel therapeutic target for the treatment of AD.
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APA 7th
Niccoli, T., Cabecinha, M., Tillmann, A., Kerr, F., Wong, C. T., Cardenes, D., et al. (2016). Increased Glucose Transport into Neurons Rescues Aβ Toxicity in Drosophila. Current biology : CB. https://doi.org/10.1016/j.cub.2016.07.017
Vancouver
Niccoli T, Cabecinha M, Tillmann A, Kerr F, Wong CT, Cardenes D, et al. Increased Glucose Transport into Neurons Rescues Aβ Toxicity in Drosophila. Current biology : CB. 2016. doi:10.1016/j.cub.2016.07.017. PMID: 27524482.
BibTeX
@article{niccoli2016-27524482,
author = {Niccoli, T. and Cabecinha, M. and Tillmann, A. and Kerr, F. and Wong, C. T. and Cardenes, D. and Vincent, A. J. and Bettedi, L. and others},
title = {{Increased Glucose Transport into Neurons Rescues Aβ Toxicity in Drosophila}},
journal = {Current biology : CB},
year = {2016},
doi = {10.1016/j.cub.2016.07.017},
pmid = {27524482},
url = {https://doi.org/10.1016/j.cub.2016.07.017}
}
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Key findings
- Disease progression is associated with a reduction in glucose transporters in both neurons and endothelial cells of the blood-brain barrier.
- This amelioration of Aβ 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.
- Our findings demonstrate a protective effect of increased neuronal uptake of glucose against Aβ toxicity and highlight Grp78 as a novel therapeutic target for the treatment of AD.
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Study details
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 23 of the 58 points we could judge it on, which is 40 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Current biology : CB) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “drosophila”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27524482) |
| Free to read | 2 / 2 | Free to read |
| Points | 23 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 58 points we could judge it on is 40 out of 100. |
| Total | 40 / 100 | — |
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