| First Author | Barroso E | Year | 2013 |
| Journal | Biochim Biophys Acta | Volume | 1832 |
| Issue | 8 | Pages | 1241-8 |
| PubMed ID | 23507144 | Mgi Jnum | J:202419 |
| Mgi Id | MGI:5519004 | Doi | 10.1016/j.bbadis.2013.03.006 |
| Citation | Barroso E, et al. (2013) Tau hyperphosphorylation and increased BACE1 and RAGE levels in the cortex of PPARbeta/delta-null mice. Biochim Biophys Acta 1832(8):1241-8 |
| abstractText | The role of peroxisome proliferator activator receptor (PPAR)beta/delta in the pathogenesis of Alzheimer's disease has only recently been explored through the use of PPARbeta/delta agonists. Here we evaluated the effects of PPARbeta/delta deficiency on the amyloidogenic pathway and tau hyperphosphorylation. PPARbeta/delta-null mice showed cognitive impairment in the object recognition task, accompanied by enhanced DNA-binding activity of NF-kappaB in the cortex and increased expression of IL-6. In addition, two NF-kappaB-target genes involved in beta-amyloid (Abeta) synthesis and deposition, the beta site APP cleaving enzyme 1 (Bace1) and the receptor for advanced glycation endproducts (Rage), respectively, increased in PPARbeta/delta-null mice compared to wild type animals. The protein levels of glial fibrillary acidic protein (GFAP) increased in the cortex of PPARbeta/delta-null mice, which would suggest the presence of astrogliosis. Finally, tau hyperphosphorylation at Ser199 and enhanced levels of PHF-tau were associated with increased levels of the tau kinases CDK5 and phospho-ERK1/2 in the cortex of PPARbeta/delta(-/-) mice. Collectively, our findings indicate that PPARbeta/delta deficiency results in cognitive impairment associated with enhanced inflammation, astrogliosis and tau hyperphosphorylation in the cortex. |
