Tau hyperphosphorylation and increased BACE1 and RAGE levels in the cortex of PPARß/d-null mice.
Por:
Barroso E, del Valle J, Porquet D, Vieira Santos AM, Salvadó L, Rodríguez-Rodríguez R, Gutiérrez P, Anglada-Huguet M, Alberch J, Camins A, Palomer FX, Pallàs M, Michalik L, Wahli W and Vazquez M
Publicada:
1 ago 2013
Resumen:
The role of peroxisome proliferator activator receptor (PPAR)ß/d in the pathogenesis of Alzheimer's disease has only recently been explored through the use of PPARß/d agonists. Here we evaluated the effects of PPARß/d deficiency on the amyloidogenic pathway and tau hyperphosphorylation. PPARß/d-null mice showed cognitive impairment in the object recognition task, accompanied by enhanced DNA-binding activity of NF-?B in the cortex and increased expression of IL-6. In addition, two NF-?B-target genes involved in ß-amyloid (Aß) synthesis and deposition, the ß site APP cleaving enzyme 1 (Bace1) and the receptor for advanced glycation endproducts (Rage), respectively, increased in PPARß/d-null mice compared to wild type animals. The protein levels of glial fibrillary acidic protein (GFAP) increased in the cortex of PPARß/d-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 PPARß/d(-/-) mice. Collectively, our findings indicate that PPARß/d deficiency results in cognitive impairment associated with enhanced inflammation, astrogliosis and tau hyperphosphorylation in the cortex.
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