Amyloid-beta (Aß1-42)-induced paralysis in Caenorhabditis elegans is reduced through NHR-49/PPARalpha.
Neurosci Lett
; 730: 135042, 2020 06 21.
Article
em En
| MEDLINE
| ID: mdl-32413539
ABSTRACT
Alzheimer´s disease is a neurodegenerative disorder characterized by the misfolding and aggregation of amyloid ß (Aß). Agonists of peroxisomal proliferator-activated receptors (PPARs) are discussed as anti-amyloidogenic compounds, e.g. due to their cholesterol-lowering activities. In a previous study we have shown in Caenorhabditis elegans expressing human Aß in muscle cells, that inhibition of steroid-signaling, by RNAi of respective members of the signaling pathway or by reducing cellular cholesterol uptake, both increases the nuclear translocation of the foxo transcription factor DAF-16 and concomitantly reduces Aß-induced paralysis. Using RNAi in the present study we show that NHR-49/PPARalpha inhibits steroidal-signaling upstream of DAF-9, a cytochrome P450-dependent enzyme which generates dafachronic acids as ligands for the nuclear hormone receptor DAF-12, and upstream of DAF-12 itself. The NHR-49/PPARalpha agonist fenofibrate reduces Aß-induced paralysis in dependence on nhr-49 and nuclear translocation of DAF-16. In conclusion, activation of NHR-49/PPARalpha inhibits the steroidal-signaling pathway which increases the nuclear translocation of DAF-16 and inhibits the Aß-induced phenotype in an Alzheimer model of C. elegans.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Regulação da Expressão Gênica
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Peptídeos beta-Amiloides
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Receptores Citoplasmáticos e Nucleares
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Proteínas de Caenorhabditis elegans
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PPAR alfa
Limite:
Animals
Idioma:
En
Revista:
Neurosci Lett
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha