| First Author | Du J | Year | 2009 |
| Journal | Biochem Biophys Res Commun | Volume | 384 |
| Issue | 3 | Pages | 357-61 |
| PubMed ID | 19422805 | Mgi Jnum | J:150592 |
| Mgi Id | MGI:3851051 | Doi | 10.1016/j.bbrc.2009.04.148 |
| Citation | Du J, et al. (2009) Antagonist of peroxisome proliferator-activated receptor gamma induces cerebellar amyloid-beta levels and motor dysfunction in APP/PS1 transgenic mice. Biochem Biophys Res Commun 384(3):357-61 |
| abstractText | Recent evidences show that peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in the modulation of the amyloid-beta (Abeta) cascade causing Alzheimer's disease (AD) and treatment with PPARgamma agonists protects against AD pathology. However, the function of PPARgamma steady-state activity in Abeta cascade and AD pathology remains unclear. In this study, an antagonist of PPARgamma, GW9662, was injected into the fourth ventricle of APP/PS1 transgenic mice to inhibit PPARgamma activity in cerebellum. The results show that inhibition of PPARgamma significantly induced Abeta levels in cerebellum and caused cerebellar motor dysfunction in APP/PS1 transgenic mice. Moreover, GW9662 treatment markedly decreased the cerebellar levels of insulin-degrading enzyme (IDE), which is responsible for the cellular degradation of Abeta. Since cerebellum is spared from significant Abeta accumulation and neurotoxicity in AD patients and animal models, these findings suggest a crucial role of PPARgamma steady-state activity in protection of cerebellum against AD pathology. |
