| First Author | Esmaeili MA | Year | 2016 |
| Journal | Hum Mol Genet | Volume | 25 |
| Issue | 2 | Pages | 317-27 |
| PubMed ID | 26604138 | Mgi Jnum | J:229164 |
| Mgi Id | MGI:5750998 | Doi | 10.1093/hmg/ddv477 |
| Citation | Esmaeili MA, et al. (2016) Preferential PPAR-alpha activation reduces neuroinflammation, and blocks neurodegeneration in vivo. Hum Mol Genet 25(2):317-27 |
| abstractText | Neuroinflammation, immune reactivity and mitochondrial abnormalities are considered as causes and/or contributors to neuronal degeneration. Peroxisome proliferator-activated receptors (PPARs) regulate both inflammatory and multiple other pathways that are implicated in neurodegeneration. In the present study, we investigated the efficacy of fenofibrate (Tricor), a pan-PPAR agonist that activates PPAR-alpha as well as other PPARs. We administered fenofibrate to superoxide dismutase 1 (SOD1(G93A)) mice daily prior to any detectable phenotypes and then animal behavior, pathology and longevity were assessed. Treated animals showed a significant slowing of the progression of disease with weight loss attenuation, enhanced motor performance, delayed onset and survival extension. Histopathological analysis of the spinal cords showed that neuronal loss was significantly attenuated in fenofibrate-treated mice. Mitochondria were preserved as indicated by Cytochrome c immunostaining in the spinal cord, which maybe partly due to increased expression of the PPAR-gamma co-activator 1-alpha. The total mRNA analysis revealed that neuroprotective and anti-inflammatory genes were elevated, while neuroinflammatory genes were down-regulated. This study demonstrates that the activation of PPAR-alpha action via fenofibrate leads to neuroprotection by both reducing neuroinflammation and protecting mitochondria, which leads to a significant increase in survival in SOD1(G93A) mice. Therefore, the development of therapeutic strategies to activate PPAR-alpha as well as other PPARs may lead to new therapeutic agents to slow or halt the progression of amyotrophic lateral sclerosis. |
