↓ Skip to main content

Mutations in LRRK2 impair NF-κB pathway in iPSC-derived neurons

Overview of attention for article published in Journal of Neuroinflammation, November 2016
Altmetric Badge

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 (83rd percentile)

Mentioned by

news
1 news outlet
twitter
1 X user

Citations

dimensions_citation
46 Dimensions

Readers on

mendeley
103 Mendeley
citeulike
1 CiteULike
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Mutations in LRRK2 impair NF-κB pathway in iPSC-derived neurons
Published in
Journal of Neuroinflammation, November 2016
DOI 10.1186/s12974-016-0761-x
Pubmed ID
Authors

Rakel López de Maturana, Valérie Lang, Amaia Zubiarrain, Amaya Sousa, Nerea Vázquez, Ana Gorostidi, Julio Águila, Adolfo López de Munain, Manuel Rodríguez, Rosario Sánchez-Pernaute

Abstract

Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to both familial and idiopathic forms of Parkinson's disease (PD). Neuroinflammation is a key event in neurodegeneration and aging, and there is mounting evidence of LRRK2 involvement in inflammatory pathways. In a previous study, we described an alteration of the inflammatory response in dermal fibroblasts from PD patients expressing the G2019S and R1441G mutations in LRRK2. Taking advantage of cellular reprogramming, we generated induced pluripotent stem cell (iPSC) lines and neurons thereafter, harboring LRRK2(G2019S) and LRRK2(R1441G) mutations. We used gene silencing and functional reporter assays to characterize the effect of the mutations. We examined the temporal profile of TNFα-induced changes in proteins of the NF-κB pathway and optimized western blot analysis to capture α-synuclein dynamics. The effects of the mutations and interventions were analyzed by two-way ANOVA tests with respect to corresponding controls. LRRK2 silencing decreased α-synuclein protein levels in mutated neurons and modified NF-κB transcriptional targets, such as PTGS2 (COX-2) and TNFAIP3 (A20). We next tested whether NF-κB and α-synuclein pathways converged and found that TNFα modulated α-synuclein levels, although we could not detect an effect of LRRK2 mutations, partly because of the individual variability. Nevertheless, we confirmed NF-κB dysregulation in mutated neurons, as shown by a protracted recovery of IκBα and a clear impairment in p65 nuclear translocation in the LRRK2 mutants. Altogether, our results show that LRRK2 mutations affect α-synuclein regulation and impair NF-κB canonical signaling in iPSC-derived neurons. TNFα modulated α-synuclein proteostasis but was not modified by the LRRK2 mutations in this paradigm. These results strengthen the link between LRRK2 and the innate immunity system underscoring the involvement of inflammatory pathways in the neurodegenerative process in PD.

X Demographics

X Demographics

The data shown below were collected from the profile of 1 X user 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 103 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 103 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 23 22%
Student > Ph. D. Student 18 17%
Student > Master 13 13%
Student > Bachelor 12 12%
Student > Doctoral Student 7 7%
Other 14 14%
Unknown 16 16%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 25 24%
Neuroscience 20 19%
Agricultural and Biological Sciences 13 13%
Medicine and Dentistry 10 10%
Pharmacology, Toxicology and Pharmaceutical Science 7 7%
Other 9 9%
Unknown 19 18%
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 06 October 2017.
All research outputs
#3,212,576
of 22,903,988 outputs
Outputs from Journal of Neuroinflammation
#643
of 2,647 outputs
Outputs of similar age
#66,008
of 415,686 outputs
Outputs of similar age from Journal of Neuroinflammation
#4
of 31 outputs
Altmetric has tracked 22,903,988 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 2,647 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one has gotten more attention than average, scoring higher than 73% 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 415,686 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 31 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 83% of its contemporaries.