| Title |
Regulation of Microglial Phagocytosis by RhoA/ROCK-Inhibiting Drugs
|
|---|---|
| Published in |
Cellular and Molecular Neurobiology, May 2016
|
| DOI | 10.1007/s10571-016-0379-7 |
| Pubmed ID | |
| Authors |
Hannah Scheiblich, Gerd Bicker |
| Abstract |
Inflammation within the central nervous system (CNS) is a major component of many neurodegenerative diseases. The underlying mechanisms of neuronal loss are not fully understood, but the activation of CNS resident phagocytic microglia seems to be a significant element contributing to neurodegeneration. At the onset of inflammation, high levels of microglial phagocytosis may serve as an essential prerequisite for creating a favorable environment for neuronal regeneration. However, the excessive and long-lasting activation of microglia and the augmented engulfment of neurons have been suggested to eventually govern widespread neurodegeneration. Here, we investigated in a functional assay of acute inflammation how the small GTPase RhoA and its main target the Rho kinase (ROCK) influence microglial phagocytosis of neuronal debris. Using BV-2 microglia and human NT2 model neurons, we demonstrate that the pain reliever Ibuprofen decreases RhoA activation and microglial phagocytosis of neuronal cell fragments. Inhibition of the downstream effector ROCK with the small-molecule agents Y-27632 and Fasudil reduces the engulfment of neuronal debris and attenuates the production of the inflammatory mediator nitric oxide during stimulation with lipopolysaccharide. Our results support a therapeutic potential for RhoA/ROCK-inhibiting agents as an effective treatment of excessive inflammation and the resulting progression of microglia-mediated neurodegeneration in the CNS. |
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.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 53 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 53 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 12 | 23% |
| Student > Ph. D. Student | 11 | 21% |
| Student > Master | 6 | 11% |
| Student > Bachelor | 4 | 8% |
| Student > Doctoral Student | 2 | 4% |
| Other | 5 | 9% |
| Unknown | 13 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 14 | 26% |
| Biochemistry, Genetics and Molecular Biology | 8 | 15% |
| Agricultural and Biological Sciences | 5 | 9% |
| Medicine and Dentistry | 3 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 4% |
| Other | 6 | 11% |
| Unknown | 15 | 28% |
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 21 May 2016.
All research outputs
#3,411,970
of 23,854,458 outputs
Outputs from Cellular and Molecular Neurobiology
#134
of 1,046 outputs
Outputs of similar age
#56,627
of 315,903 outputs
Outputs of similar age from Cellular and Molecular Neurobiology
#2
of 19 outputs
Altmetric has tracked 23,854,458 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 1,046 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one has done well, scoring higher than 85% 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 315,903 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 81% of its contemporaries.
We're also able to compare this research output to 19 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 89% of its contemporaries.