| Title |
Pan-PPAR Modulation Effectively Protects APP/PS1 Mice from Amyloid Deposition and Cognitive Deficits
|
|---|---|
| Published in |
Molecular Neurobiology, May 2014
|
| DOI | 10.1007/s12035-014-8743-4 |
| Pubmed ID | |
| Authors |
Markus P. Kummer, Rafael Schwarzenberger, Sakina Sayah-Jeanne, Mathieu Dubernet, Robert Walczak, Dean W. Hum, Stephanie Schwartz, Daisy Axt, Michael T. Heneka |
| Abstract |
Alzheimer's disease (AD) is a neurodegenerative condition that leads to neuronal death and memory dysfunction. In the past, specific peroxisome proliferator-activated receptor (PPAR)γ-agonists, such as pioglitazone, have been tested with limited success to improve AD pathology. Here, we investigated the therapeutic efficacy of GFT1803, a novel potent PPAR agonist that activates all the three PPAR isoforms (α/δ/γ) in the APP/PS1 mouse model in comparison to the selective PPARγ-agonist pioglitazone. Both compounds showed similar brain/plasma partitioning ratios, although whole body and brain exposure to GFT1803 was significantly lower as compared to pioglitazone, at doses used in this study. Oral treatment of APP/PS1 mice with GFT1803 decreased microglial activation, amyloid β (Aβ) plaque area, Aβ levels in sodium dodecyl sulfate- and formic acid-soluble fractions in a concentration-dependent manner. With a single exception of Aβ38 and Aβ40 levels, measured by ELISA, these effects were not observed in mice treated with pioglitazone. Both ligands decreased glial fibrillary acidic protein (GFAP) expression to similar extent and did not affect ApoE expression. Finally, GFT1803 increased insulin-degrading enzyme expression. Analysis of spatial memory formation in the Morris water maze demonstrated that both compounds were able to partially revert the phenotype of APP/PS1 mice in comparison to wild-type mice with GFT1803 being most effective. As compared to pioglitazone, GFT1803 (pan-PPAR agonist) produced both quantitatively superior and qualitatively different therapeutic effects with respect to amyloid plaque burden, insoluble Aβ content, and neuroinflammation at significantly lower whole body and brain exposure rates. |
X Demographics
The data shown below were collected from the profiles of 16 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 4 | 25% |
| Monaco | 1 | 6% |
| Unknown | 11 | 69% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 16 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 62 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 2% |
| Unknown | 61 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 8 | 13% |
| Student > Master | 8 | 13% |
| Student > Ph. D. Student | 7 | 11% |
| Student > Bachelor | 5 | 8% |
| Student > Doctoral Student | 4 | 6% |
| Other | 10 | 16% |
| Unknown | 20 | 32% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 10 | 16% |
| Neuroscience | 7 | 11% |
| Agricultural and Biological Sciences | 5 | 8% |
| Biochemistry, Genetics and Molecular Biology | 4 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 6% |
| Other | 10 | 16% |
| Unknown | 22 | 35% |
Attention Score in Context
This research output has an Altmetric Attention Score of 14. 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 07 April 2015.
All research outputs
#2,274,175
of 22,756,196 outputs
Outputs from Molecular Neurobiology
#252
of 3,436 outputs
Outputs of similar age
#24,367
of 227,399 outputs
Outputs of similar age from Molecular Neurobiology
#9
of 53 outputs
Altmetric has tracked 22,756,196 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,436 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one has done particularly well, scoring higher than 92% 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 227,399 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 89% of its contemporaries.
We're also able to compare this research output to 53 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.