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LRRK2 activity does not dramatically alter α-synuclein pathology in primary neurons

Overview of attention for article published in Acta Neuropathologica Communications, May 2018
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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 (89th percentile)

Mentioned by

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2 news outlets
twitter
10 tweeters

Citations

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15 Dimensions

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46 Mendeley
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1 CiteULike
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Title
LRRK2 activity does not dramatically alter α-synuclein pathology in primary neurons
Published in
Acta Neuropathologica Communications, May 2018
DOI 10.1186/s40478-018-0550-0
Pubmed ID
Authors

Michael X. Henderson, Chao Peng, John Q. Trojanowski, Virginia M. Y. Lee

Abstract

Mutations in leucine-rich repeat kinase (LRRK2) are the most common cause of heritable Parkinson's disease (PD), and the most common mutations in LRRK2 lead to elevated kinase activity. For these reasons, inhibitors targeting LRRK2 have been the subject of intense research and development. However, it has been difficult to develop preclinical models that recapitulate PD-relevant LRRK2 phenotypes. The primary pathology in PD is the Lewy body (LB), which is a cytoplasmic aggregate of α-synuclein. The recent demonstration that LB-like aggregates of α-synuclein can be induced in primary neurons has provided a robust model for testing genetic modifiers of PD-relevant aggregation and neurodegeneration. In this study, we test the modulation of α-synuclein pathology by LRRK2 in primary neuron cultures using biochemistry and immunocytochemistry. We find that expression of familial mutant G2019S LRRK2 does not dramatically elevate the pathological burden of α-synuclein or neurodegeneration in neurons. We further test three LRRK2 inhibitors in two strains of wildtype neurons and find that even robust LRRK2 inhibition is insufficient to reduce α-synuclein pathology. LRRK2 inhibitors similarly had no effect in neurons with α-synuclein pathology seeded by human brain-derived pathological α-synuclein. Finally, we find that this lack of pathological modulation by LRRK2 was not confined to hippocampal neurons, but was also absent in midbrain dopaminergic neuron cultures. These data demonstrate that LRRK2 activity does not have more than minor effects on α-synuclein pathology in primary neurons, and more complex models may be needed to evaluate the ability of LRRK2 inhibitors to treat PD.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 46 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 13 28%
Researcher 8 17%
Student > Postgraduate 5 11%
Student > Master 5 11%
Student > Bachelor 3 7%
Other 6 13%
Unknown 6 13%
Readers by discipline Count As %
Neuroscience 15 33%
Agricultural and Biological Sciences 9 20%
Biochemistry, Genetics and Molecular Biology 7 15%
Medicine and Dentistry 6 13%
Immunology and Microbiology 1 2%
Other 3 7%
Unknown 5 11%

Attention Score in Context

This research output has an Altmetric Attention Score of 22. 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 21 February 2020.
All research outputs
#922,621
of 15,685,682 outputs
Outputs from Acta Neuropathologica Communications
#64
of 915 outputs
Outputs of similar age
#28,819
of 280,919 outputs
Outputs of similar age from Acta Neuropathologica Communications
#1
of 1 outputs
Altmetric has tracked 15,685,682 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 915 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.4. This one has done particularly well, scoring higher than 92% 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 280,919 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 89% 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