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Membrane binding, internalization, and sorting of alpha-synuclein in the cell

Overview of attention for article published in Acta Neuropathologica Communications, August 2018
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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 (85th percentile)

Mentioned by

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1 news outlet
twitter
10 tweeters

Citations

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42 Dimensions

Readers on

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84 Mendeley
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1 CiteULike
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Title
Membrane binding, internalization, and sorting of alpha-synuclein in the cell
Published in
Acta Neuropathologica Communications, August 2018
DOI 10.1186/s40478-018-0578-1
Pubmed ID
Authors

Caterina Masaracchia, Marilena Hnida, Ellen Gerhardt, Tomás Lopes da Fonseca, Anna Villar-Pique, Tiago Branco, Markus A. Stahlberg, Camin Dean, Claudio O. Fernández, Ira Milosevic, Tiago F. Outeiro

Abstract

Alpha-synuclein (aSyn) plays a crucial role in Parkinson's disease (PD) and other synucleinopathies, since it misfolds and accumulates in typical proteinaceous inclusions. While the function of aSyn is thought to be related to vesicle binding and trafficking, the precise molecular mechanisms linking aSyn with synucleinopathies are still obscure. aSyn can spread in a prion-like manner between interconnected neurons, contributing to the propagation of the pathology and to the progressive nature of synucleinopathies. Here, we investigated the interaction of aSyn with membranes and trafficking machinery pathways using cellular models of PD that are amenable to detailed molecular analyses. We found that different species of aSyn can enter cells and form high molecular weight species, and that membrane binding properties are important for the internalization of aSyn. Once internalized, aSyn accumulates in intracellular inclusions. Interestingly, we found that internalization is blocked in the presence of dynamin inhibitors (blocked membrane scission), suggesting the involvement of the endocytic pathway in the internalization of aSyn. By screening a pool of small Rab-GTPase proteins (Rabs) which regulate membrane trafficking, we found that internalized aSyn partially colocalized with Rab5A and Rab7. Initially, aSyn accumulated in Rab4A-labelled vesicles and, at later stages, it reached the autophagy-lysosomal pathway (ALP) where it gets degraded. In total, our study emphasizes the importance of membrane binding, not only as part of the normal function but also as an important step in the internalization and subsequent accumulation of aSyn. Importantly, we identified a fundamental role for Rab proteins in the modulation of aSyn processing, clearance and spreading, suggesting that targeting Rab proteins may hold important therapeutic value in PD and other synucleinopathies.

Twitter Demographics

The data shown below were collected from the profiles of 10 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 84 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 84 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 24 29%
Researcher 14 17%
Student > Master 11 13%
Student > Bachelor 9 11%
Other 3 4%
Other 8 10%
Unknown 15 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 19 23%
Neuroscience 17 20%
Agricultural and Biological Sciences 12 14%
Medicine and Dentistry 6 7%
Chemistry 5 6%
Other 7 8%
Unknown 18 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 14. 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 07 June 2019.
All research outputs
#1,333,232
of 15,184,505 outputs
Outputs from Acta Neuropathologica Communications
#140
of 854 outputs
Outputs of similar age
#33,302
of 229,326 outputs
Outputs of similar age from Acta Neuropathologica Communications
#1
of 1 outputs
Altmetric has tracked 15,184,505 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 854 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 10.0. This one has done well, scoring higher than 83% 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 229,326 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 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them