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Aβ-Induced Insulin Resistance and the Effects of Insulin on the Cholesterol Synthesis Pathway and Aβ Secretion in Neural Cells

Overview of attention for article published in Neuroscience Bulletin, May 2016
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (83rd percentile)
  • High Attention Score compared to outputs of the same age and source (84th percentile)

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1 news outlet
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Citations

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48 Mendeley
Title
Aβ-Induced Insulin Resistance and the Effects of Insulin on the Cholesterol Synthesis Pathway and Aβ Secretion in Neural Cells
Published in
Neuroscience Bulletin, May 2016
DOI 10.1007/s12264-016-0034-9
Pubmed ID
Authors

Dema Najem, Michelle Bamji-Mirza, Ze Yang, Wandong Zhang

Abstract

Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) toxicity, tau pathology, insulin resistance, neuroinflammation, and dysregulation of cholesterol homeostasis, all of which play roles in neurodegeneration. Insulin has polytrophic effects on neurons and may be at the center of these pathophysiological changes. In this study, we investigated possible relationships among insulin signaling and cholesterol biosynthesis, along with the effects of Aβ42 on these pathways in vitro. We found that neuroblastoma 2a (N2a) cells transfected with the human gene encoding amyloid-β protein precursor (AβPP) (N2a-AβPP) produced Aβ and exhibited insulin resistance by reduced p-Akt and a suppressed cholesterol-synthesis pathway following insulin treatment, and by increased phosphorylation of insulin receptor subunit-1 at serine 612 (p-IRS-S612) as compared to parental N2a cells. Treatment of human neuroblastoma SH-SY5Y cells with Aβ42 also increased p-IRS-S612, suggesting that Aβ42 is responsible for insulin resistance. The insulin resistance was alleviated when N2a-AβPP cells were treated with higher insulin concentrations. Insulin increased Aβ release from N2a-AβPP cells, by which it may promote Aβ clearance. Insulin increased cholesterol-synthesis gene expression in SH-SY5Y and N2a cells, including 24-dehydrocholesterol reductase (DHCR24) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) through sterol-regulatory element-binding protein-2 (SREBP2). While Aβ42-treated SH-SY5Y cells exhibited increased HMGCR expression and c-Jun phosphorylation as pro-inflammatory responses, they also showed down-regulation of neuro-protective/anti-inflammatory DHCR24. These results suggest that Aβ42 may cause insulin resistance, activate JNK for c-Jun phosphorylation, and lead to dysregulation of cholesterol homeostasis, and that enhancing insulin signaling may relieve the insulin-resistant phenotype and the dysregulated cholesterol-synthesis pathway to promote Aβ release for clearance from neural cells.

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The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 48 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 19%
Student > Bachelor 7 15%
Student > Master 7 15%
Researcher 4 8%
Student > Doctoral Student 3 6%
Other 6 13%
Unknown 12 25%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 23%
Neuroscience 10 21%
Medicine and Dentistry 7 15%
Pharmacology, Toxicology and Pharmaceutical Science 3 6%
Agricultural and Biological Sciences 1 2%
Other 3 6%
Unknown 13 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 May 2016.
All research outputs
#2,950,957
of 22,873,031 outputs
Outputs from Neuroscience Bulletin
#68
of 773 outputs
Outputs of similar age
#53,052
of 333,293 outputs
Outputs of similar age from Neuroscience Bulletin
#2
of 13 outputs
Altmetric has tracked 22,873,031 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 773 research outputs from this source. They receive a mean Attention Score of 4.0. This one has done well, scoring higher than 89% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 333,293 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 83% of its contemporaries.
We're also able to compare this research output to 13 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.