Tau hyperphosphorylation and increased BACE1 and RAGE levels in the cortex of PPARβ/δ-null mice.

Details

Serval ID
serval:BIB_497583315802
Type
Article: article from journal or magazin.
Collection
Publications
Title
Tau hyperphosphorylation and increased BACE1 and RAGE levels in the cortex of PPARβ/δ-null mice.
Journal
Biochimica et Biophysica Acta. Molecular Basis of Disease
Author(s)
Barroso E., del Valle J., Porquet D., Vieira Santos A.M., Salvadó L., Rodríguez-Rodríguez R., Gutiérrez P., Anglada-Huguet M., Alberch J., Camins A., Palomer X., Pallàs M., Michalik L., Wahli W., Vázquez-Carrera M.
ISSN
0925-4439
ISSN-L
1879-260X
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
1832
Number
8
Pages
1241-1248
Language
english
Abstract
The 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.
Keywords
PPAR beta/delta, BACE1, RAGE, Tau, ERK1/2, Cortex
Pubmed
Web of science
Open Access
Yes
Create date
14/08/2013 10:49
Last modification date
20/08/2019 14:56
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