Tau hyperphosphorylation and increased BACE1 and RAGE levels in the cortex of PPARß/δ-null mice.
Biochim Biophys Acta
; 1832(8): 1241-8, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23507144
ABSTRACT
The role of peroxisome proliferator activator receptor (PPAR)ß/δ in the pathogenesis of Alzheimer's disease has only recently been explored through the use of PPARß/δ agonists. Here we evaluated the effects of PPARß/δ deficiency on the amyloidogenic pathway and tau hyperphosphorylation. PPARß/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 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/δ-null mice compared to wild type animals. The protein levels of glial fibrillary acidic protein (GFAP) increased in the cortex of PPARß/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 PPARß/δ(-/-) mice. Collectively, our findings indicate that PPARß/δ deficiency results in cognitive impairment associated with enhanced inflammation, astrogliosis and tau hyperphosphorylation in the cortex.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Imunológicos
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Córtex Cerebral
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Ácido Aspártico Endopeptidases
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Proteínas tau
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PPAR beta
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Secretases da Proteína Precursora do Amiloide
Limite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Espanha