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Lack of additive role of ageing in nigrostriatal neurodegeneration triggered by α-synuclein overexpression

Overview of attention for article published in Acta Neuropathologica Communications, July 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (85th percentile)
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

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1 news outlet
twitter
2 tweeters

Citations

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80 Dimensions

Readers on

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132 Mendeley
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2 CiteULike
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Title
Lack of additive role of ageing in nigrostriatal neurodegeneration triggered by α-synuclein overexpression
Published in
Acta Neuropathologica Communications, July 2015
DOI 10.1186/s40478-015-0222-2
Pubmed ID
Authors

Mathieu Bourdenx, Sandra Dovero, Michel Engeln, Simone Bido, Matthieu F. Bastide, Nathalie Dutheil, Isabel Vollenweider, Laetitia Baud, Camille Piron, Virginie Grouthier, Thomas Boraud, Grégory Porras, Qin Li, Veerle Baekelandt, Dieter Scheller, Anne Michel, Pierre-Olivier Fernagut, François Georges, Grégoire Courtine, Erwan Bezard, Benjamin Dehay

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons as well as the presence of proteinaceous inclusions named Lewy bodies. α-synuclein (α-syn) is a major constituent of Lewy bodies, and the first disease-causing protein characterized in PD. Several α-syn-based animal models of PD have been developed to investigate the pathophysiology of PD, but none of them recapitulate the full picture of the disease. Ageing is the most compelling and major risk factor for developing PD but its impact on α-syn toxicity remains however unexplored. In this study, we developed and exploited a recombinant adeno-associated viral (AAV) vector of serotype 9 overexpressing mutated α-syn to elucidate the influence of ageing on the dynamics of PD-related neurodegeneration associated with α-syn pathology in different mammalian species. Identical AAV pseudotype 2/9 vectors carrying the DNA for human mutant p.A53T α-syn were injected into the substantia nigra to induce neurodegeneration and synucleinopathy in mice, rats and monkeys. Rats were used first to validate the ability of this serotype to replicate α-syn pathology and second to investigate the relationship between the kinetics of α-syn-induced nigrostriatal degeneration and the progressive onset of motor dysfunctions, strikingly reminiscent of the impairments observed in PD patients. In mice, AAV2/9-hα-syn injection into the substantia nigra was associated with accumulation of α-syn and phosphorylated hα-syn, regardless of mouse strain. However, phenotypic mutants with either accelerated senescence or resistance to senescence did not display differential susceptibility to hα-syn overexpression. Of note, p-α-syn levels correlated with nigrostriatal degeneration in mice. In monkeys, hα-syn-induced degeneration of the nigrostriatal pathway was not affected by the age of the animals. Unlike mice, monkeys did not exhibit correlations between levels of phosphorylated α-syn and neurodegeneration. In conclusion, AAV2/9-mediated hα-syn induces robust nigrostriatal neurodegeneration in mice, rats and monkeys, allowing translational comparisons among species. Ageing, however, neither exacerbated nigrostriatal neurodegeneration nor α-syn pathology per se. Our unprecedented multi-species investigation thus favours the multiple-hit hypothesis for PD wherein ageing would merely be an aggravating, additive, factor superimposed upon an independent disease process.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 132 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 <1%
France 1 <1%
Unknown 130 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 21 16%
Researcher 20 15%
Student > Master 15 11%
Student > Bachelor 11 8%
Student > Doctoral Student 10 8%
Other 28 21%
Unknown 27 20%
Readers by discipline Count As %
Neuroscience 39 30%
Agricultural and Biological Sciences 19 14%
Biochemistry, Genetics and Molecular Biology 9 7%
Medicine and Dentistry 9 7%
Engineering 5 4%
Other 14 11%
Unknown 37 28%

Attention Score in Context

This research output has an Altmetric Attention Score of 11. 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 23 April 2016.
All research outputs
#2,878,345
of 22,818,766 outputs
Outputs from Acta Neuropathologica Communications
#560
of 1,374 outputs
Outputs of similar age
#38,627
of 263,272 outputs
Outputs of similar age from Acta Neuropathologica Communications
#11
of 21 outputs
Altmetric has tracked 22,818,766 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,374 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.9. This one has gotten more attention than average, scoring higher than 57% 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 263,272 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 85% of its contemporaries.
We're also able to compare this research output to 21 others from the same source and published within six weeks on either side of this one. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.