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Inhibition of the hepatic Nlrp3 protects dopaminergic neurons via attenuating systemic inflammation in a MPTP/p mouse model of Parkinson’s disease

Overview of attention for article published in Journal of Neuroinflammation, July 2018
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Title
Inhibition of the hepatic Nlrp3 protects dopaminergic neurons via attenuating systemic inflammation in a MPTP/p mouse model of Parkinson’s disease
Published in
Journal of Neuroinflammation, July 2018
DOI 10.1186/s12974-018-1236-z
Pubmed ID
Authors

Chen Qiao, Qian Zhang, Qingling Jiang, Ting Zhang, Miaomiao Chen, Yi Fan, Jianhua Ding, Ming Lu, Gang Hu

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder with progressive loss of dopaminergic (DA) neurons. Systemic inflammation is shown to initiate and exacerbate DA neuronal degeneration in the substantia nigra. The infiltration and transformation of immune cells from the peripheral tissues are detected in and around the affected brain regions of PD patients. Our previous studies demonstrated the crucial role that microglial Nod-like receptor protein (NLRP) 3 inflammasome plays in the pathogenesis of PD. Nevertheless, the direct linkage between peripheral inflammation and DA neuron death remains obscure. In the present study, we detected the NLRP3 expressions in the midbrain, liver, and bone marrow-derived macrophages in response to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) acute and chronic challenge. We then used a tail vein injection of Nlrp3-siRNA wrapped with lentivirus to explore the potential influence of hepatic NLRP3 inflammasome-mediated inflammation on neuronal injury in a mouse model of PD via immunohistochemistry, ELISA, and Western blotting analysis. We showed that siNlrp3 downregulated the NLRP3 protein expression and inhibited the activation of NLRP3 inflammasomes in mice livers. The tail vein injection of LV3-siNlrp3 reduced the liver pro-inflammatory cytokine production, which subsequently alleviated MPTP-triggered microglial activation and DA neuron loss in the midbrain. These findings indicated that inhibition of hepatic NLRP3 inflammasome weakens inflammatory cytokines spreading into the brain and delays the progress of neuroinflammation and DA neuronal degeneration. This study gives us an insight into the direct linkage between liver inflammation and DA neuron damage in the pathogenesis of PD and provides the potential target of NLRP3 for developing novel drugs for PD therapy.

Twitter Demographics

The data shown below were collected from the profiles of 3 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 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 49 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 11 22%
Student > Master 8 16%
Student > Ph. D. Student 7 14%
Student > Bachelor 4 8%
Other 2 4%
Other 7 14%
Unknown 10 20%
Readers by discipline Count As %
Neuroscience 15 31%
Medicine and Dentistry 8 16%
Biochemistry, Genetics and Molecular Biology 4 8%
Pharmacology, Toxicology and Pharmaceutical Science 4 8%
Agricultural and Biological Sciences 3 6%
Other 3 6%
Unknown 12 24%

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 10 July 2018.
All research outputs
#10,508,890
of 13,801,769 outputs
Outputs from Journal of Neuroinflammation
#1,062
of 1,613 outputs
Outputs of similar age
#186,630
of 271,002 outputs
Outputs of similar age from Journal of Neuroinflammation
#1
of 1 outputs
Altmetric has tracked 13,801,769 research outputs across all sources so far. This one is in the 20th percentile – i.e., 20% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,613 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.2. This one is in the 27th percentile – i.e., 27% of its peers scored the same or lower than it.
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