Caprylic acid attenuates amyloid-ß proteotoxicity by supplying energy via ß-oxidation in an Alzheimer's disease model of the nematode Caenorhabditis elegans.
Nutr Neurosci
; 27(3): 252-261, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-36800228
ABSTRACT
Computer-based analysis of motility was used as a measure of amyloid-ß (Aß) proteotoxicity in the transgenic strain GMC101, expressing human Aß1-42 in body wall muscle cells. Aß-aggregation was quantified to relate the effects of caprylic acid (CA) to the amount of the proteotoxic protein. Gene knockdowns were induced through RNA-interference (RNAi). Moreover, the estimation of adenosine triphosphate (ATP) levels, the mitochondrial membrane potential (MMP) and oxygen consumption served the evaluation of mitochondrial function. CA improved the motility of GMC101 nematodes and reduced Aß aggregation. Whereas RNAi for orthologues encoding key enzymes for α-lipoic acid and ketone bodies synthesis did not affect motility stimulation by CA, knockdown of orthologues involved in ß-oxidation of fatty acids diminished its effects. The efficient energy gain by application of CA was finally proven by the increase of ATP levels in association with increased oxygen consumption and MMP. In conclusion, CA attenuates Aß proteotoxicity by supplying energy via FAO. Since especially glucose oxidation is disturbed in Alzheimer´s disease, CA could potentially serve as an alternative energy fuel.
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Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Caenorhabditis elegans
/
Doença de Alzheimer
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nutr Neurosci
Assunto da revista:
CIENCIAS DA NUTRICAO
/
NEUROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Alemanha