Tau hyperphosphorylation and increased BACE1 and RAGE levels in the cortex of PPARβ/δ-null mice
2013; Elsevier BV; Volume: 1832; Issue: 8 Linguagem: Inglês
10.1016/j.bbadis.2013.03.006
ISSN1879-260X
AutoresEmma Barroso, Jaume del Valle, David Porquet, Ana M. Vieira Santos, Laia Salvadó, Rosalía Rodríguez‐Rodríguez, Patrícia Gutiérrez, Marta Anglada‐Huguet, Jordi Alberch, Antoni Camins, Xavier Palomer, Mercé Pallás, Liliane Michalik, Walter Wahli, Manuel Vázquez‐Carrera,
Tópico(s)Peroxisome Proliferator-Activated Receptors
ResumoThe role of peroxisome proliferator activator receptor (PPAR)β/δ in the pathogenesis of Alzheimer's disease has only recently been explored through the use of PPARβ/δ agonists. Here we evaluated the effects of PPARβ/δ deficiency on the amyloidogenic pathway and tau hyperphosphorylation. PPARβ/δ-null mice showed cognitive impairment in the object recognition task, accompanied by enhanced DNA-binding activity of NF-κB in the cortex and increased expression of IL-6. In addition, two NF-κB-target genes involved in β-amyloid (Aβ) synthesis and deposition, the β site APP cleaving enzyme 1 (Bace1) and the receptor for advanced glycation endproducts (Rage), respectively, increased in PPARβ/δ-null mice compared to wild type animals. The protein levels of glial fibrillary acidic protein (GFAP) increased in the cortex of PPARβ/δ-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 PPARβ/δ(-/-) mice. Collectively, our findings indicate that PPARβ/δ deficiency results in cognitive impairment associated with enhanced inflammation, astrogliosis and tau hyperphosphorylation in the cortex.
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