| Title |
Mechanism of Action for NNZ-2566 Anti-inflammatory Effects Following PBBI Involves Upregulation of Immunomodulator ATF3
|
|---|---|
| Published in |
NeuroMolecular Medicine, June 2013
|
| DOI | 10.1007/s12017-013-8236-z |
| Pubmed ID | |
| Authors |
Casandra M. Cartagena, Katie L. Phillips, Garry L. Williams, Melissa Konopko, Frank C. Tortella, Jitendra R. Dave, Kara E. Schmid |
| Abstract |
The tripeptide glycine-proline-glutamate analogue NNZ-2566 (Neuren Pharmaceuticals) demonstrates neuroprotective efficacy in models of traumatic brain injury. In penetrating ballistic-like brain injury (PBBI), it significantly decreases injury-induced upregulation of inflammatory cytokines including TNF-α, IFN-γ, and IL-6. However, the mechanism by which NNZ-2566 acts has yet to be determined. The activating transcription factor-3 (ATF3) is known to repress expression of these inflammatory cytokines and was increased at the mRNA and protein level 24-h post-PBBI. This study investigated whether 12 h of NNZ-2566 treatment following PBBI alters atf3 expression. PBBI alone significantly increased atf3 mRNA levels by 13-fold at 12 h and these levels were increased by an additional fourfold with NNZ-2566 treatment. To confirm that changes in mRNA translated to changes in protein expression, ATF3 expression levels were determined in vivo in microglia/macrophages, T cells, natural killer cells (NKCs), astrocytes, and neurons. PBBI alone significantly increased ATF3 in microglia/macrophages (820%), NKCs (58%), and astrocytes (51%), but decreased levels in T cells (48%). NNZ-2566 treatment further increased ATF3 protein expression in microglia/macrophages (102%), NKCs (308%), and astrocytes (13%), while reversing ATF3 decreases in T cells. Finally, PBBI increased ATF3 levels by 55% in neurons and NNZ-2566 treatment further increased these levels an additional 33%. Since increased ATF3 may be an innate protective mechanism to limit inflammation following injury, these results demonstrating that the anti-inflammatory and neuroprotective drug NNZ-2566 increase both mRNA and protein levels of ATF3 in multiple cell types provide a cellular mechanism for NNZ-2566 modulation of neuroinflammation following PBBI. |
Mendeley readers
The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Chile | 1 | 4% |
| Unknown | 24 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 20% |
| Student > Master | 4 | 16% |
| Student > Doctoral Student | 2 | 8% |
| Student > Ph. D. Student | 2 | 8% |
| Professor | 2 | 8% |
| Other | 4 | 16% |
| Unknown | 6 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 6 | 24% |
| Agricultural and Biological Sciences | 5 | 20% |
| Medicine and Dentistry | 4 | 16% |
| Psychology | 1 | 4% |
| Nursing and Health Professions | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 7 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 9. 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 17 February 2021.
All research outputs
#3,720,274
of 22,721,584 outputs
Outputs from NeuroMolecular Medicine
#90
of 446 outputs
Outputs of similar age
#32,559
of 198,005 outputs
Outputs of similar age from NeuroMolecular Medicine
#2
of 6 outputs
Altmetric has tracked 22,721,584 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 446 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.3. This one has done well, scoring higher than 79% 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 198,005 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 6 others from the same source and published within six weeks on either side of this one. This one has scored higher than 4 of them.