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Identification of a specific α-synuclein peptide (α-Syn 29-40) capable of eliciting microglial superoxide production to damage dopaminergic neurons

Overview of attention for article published in Journal of Neuroinflammation, June 2016
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (78th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (60th percentile)

Mentioned by

news
1 news outlet

Citations

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16 Dimensions

Readers on

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33 Mendeley
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Title
Identification of a specific α-synuclein peptide (α-Syn 29-40) capable of eliciting microglial superoxide production to damage dopaminergic neurons
Published in
Journal of Neuroinflammation, June 2016
DOI 10.1186/s12974-016-0606-7
Pubmed ID
Authors

Shijun Wang, Chun-Hsien Chu, Mingri Guo, Lulu Jiang, Hui Nie, Wei Zhang, Belinda Wilson, Li Yang, Tessandra Stewart, Jau-Shyong Hong, Jing Zhang

Abstract

Misfolded α-synuclein (α-Syn) aggregates participate in the pathogenesis of synucleinopathies, such as Parkinson's disease. Whereas much is known about how the various domains within full-length α-Syn (FL-α-Syn) contribute to the formation of α-Syn aggregates and therefore to their neurotoxicity, little is known about whether the individual peptides that can be generated from α-syn, possibly as intermediate metabolites during degradation of misfolded α-Syn aggregates, are neurotoxic themselves. A series of synthesized α-Syn peptides, corresponding to the locus in FL-α-Syn containing alanine 30, substitution of which with a proline causes a familial form of Parkinson's disease, were examined for their capacity of inducing release of microglial superoxide. The neurotoxicity of these peptides was measured according to their influence on the ability of neuroglial cultures deficient in gp91 (phox) , the catalytic unit of NADPH oxidase (Nox2), or wild-type cultures to take up (3)H-labeled dopamine and on the number of tyrosine hydroxylase-staining-positive neurons. Western blots and confocal images were utilized to analyze membrane translocation of p47 (phox) and p67 (phox) , phosphorylation of p47 (phox) and Erk1/2 kinase, and binding of α-Syn peptides to gp91 (phox) . Activation of brain microglia in mice injected with α-Syn peptides was demonstrated by immunostaining for major histocompatibility complex (MHC)-II along with qPCR for Iba-1 and MHC-II. We report α-Syn (29-40) as a specific peptide capable of activating microglial Nox2 to produce superoxide and cause dopaminergic neuronal damage. Administered to mice, this peptide also activated brain microglia to increase expression of MHC-II and Iba-1 and stimulated oxidation reaction. Exploring the underlying mechanisms showed that α-Syn (29-40) peptide triggered Nox2 to generate extracellular superoxide and its metabolite H2O2 by binding to the catalytic unit gp91 (phox) of Nox2; diffusing into cytosol, H2O2 activated Erk1/2 kinase to phosphorylate p47 (phox) and p67 (phox) and further activated Nox2, establishing a positive feedback loop to amplify the Nox2-mediated response. Collectively, our study suggests novel information regarding how α-Syn causes neuronal injury, possibly including mechanisms involving abnormal metabolites of α-Syn aggregates.

Mendeley readers

The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 33 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 13 39%
Student > Postgraduate 3 9%
Student > Master 3 9%
Student > Bachelor 3 9%
Student > Doctoral Student 2 6%
Other 3 9%
Unknown 6 18%
Readers by discipline Count As %
Neuroscience 8 24%
Agricultural and Biological Sciences 5 15%
Biochemistry, Genetics and Molecular Biology 3 9%
Medicine and Dentistry 3 9%
Pharmacology, Toxicology and Pharmaceutical Science 3 9%
Other 4 12%
Unknown 7 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. 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 24 June 2016.
All research outputs
#1,106,235
of 7,940,332 outputs
Outputs from Journal of Neuroinflammation
#188
of 1,010 outputs
Outputs of similar age
#52,125
of 262,111 outputs
Outputs of similar age from Journal of Neuroinflammation
#23
of 63 outputs
Altmetric has tracked 7,940,332 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,010 research outputs from this source. They receive a mean Attention Score of 4.8. This one has done well, scoring higher than 78% 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 262,111 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 78% of its contemporaries.
We're also able to compare this research output to 63 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.