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α-Synuclein disrupts the anti-inflammatory role of Drd2 via interfering β-arrestin2-TAB1 interaction in astrocytes

Overview of attention for article published in Journal of Neuroinflammation, September 2018
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Title
α-Synuclein disrupts the anti-inflammatory role of Drd2 via interfering β-arrestin2-TAB1 interaction in astrocytes
Published in
Journal of Neuroinflammation, September 2018
DOI 10.1186/s12974-018-1302-6
Pubmed ID
Authors

Ren-Hong Du, Yan Zhou, Mei-Ling Xia, Ming Lu, Jian-Hua Ding, Gang Hu

Abstract

α-Synuclein (α-Syn)-induced neuroinflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD). Dopamine D2 receptor (Drd2) has been regarded as a potential anti-inflammatory target in the therapy of neurodegenerative diseases. However, the effect of astrocytic Drd2 in α-Syn-induced neuroinflammation remains unclear. The effect of Drd2 on neuroinflammation was examined in mouse primary astrocyte in vitro and A53T transgenic mice in vivo. The inflammatory responses of astrocyte were detected using immunofluorescence, ELISA, and qRT-PCR. The details of molecular mechanism were assessed using Western blotting and protein-protein interaction assays. We showed that the selective Drd2 agonist quinpirole suppressed inflammation in the midbrain of wild-type mice, but not in α-Syn-overexpressed mice. We also found that Drd2 agonists significantly alleviated LPS-induced inflammatory response in astrocytes, but failed to suppress α-Syn-induced inflammatory response. The anti-inflammation effect of Drd2 was dependent on β-arrestin2-mediated signaling, but not classical G protein pathway. α-Syn reduced the expression of β-arrestin2 in astrocytes. Increased the β-arrestin2 expression restored in the anti-inflammation of Drd2 in α-Syn-induced inflammation. Furthermore, we demonstrated that α-Syn disrupted the anti-inflammation of Drd2 via inhibiting the association of β-arrestin2 with transforming growth factor-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) and promoting TAK1-TAB1 interaction in astrocytes. Our study illustrates that astrocytic Drd2 inhibits neuroinflammation through a β-arrestin2-dependent mechanism and provides a new strategy for treatment of PD. Our findings also reveal that α-Syn disrupts the function of β-arrestin2 and inflammatory pathways in the pathogenesis of PD.

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 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 44 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 9 20%
Student > Ph. D. Student 8 18%
Student > Master 6 14%
Other 3 7%
Student > Bachelor 3 7%
Other 4 9%
Unknown 11 25%
Readers by discipline Count As %
Neuroscience 14 32%
Pharmacology, Toxicology and Pharmaceutical Science 6 14%
Agricultural and Biological Sciences 5 11%
Biochemistry, Genetics and Molecular Biology 3 7%
Medicine and Dentistry 2 5%
Other 1 2%
Unknown 13 30%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 12 September 2018.
All research outputs
#10,744,135
of 13,505,974 outputs
Outputs from Journal of Neuroinflammation
#1,132
of 1,573 outputs
Outputs of similar age
#198,422
of 264,550 outputs
Outputs of similar age from Journal of Neuroinflammation
#1
of 2 outputs
Altmetric has tracked 13,505,974 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,573 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one is in the 15th percentile – i.e., 15% of its peers scored the same or lower than it.
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 264,550 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 13th percentile – i.e., 13% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 2 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