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Título
SERCA inhibition improves lifespan and healthspan in a chemical model of Parkinson disease in Caenorhabditis elegans
Autor
Año del Documento
2023
Editorial
Frontiers
Descripción
Producción Científica
Documento Fuente
Frontiers in Pharmacology, May 2023, 14, 1182428
Résumé
Introduction: The high prevalence of neurodegenerative diseases in our population and the lack of effective treatments encourage the search for new therapeutic targets for these pathologies. We have recently described that submaximal inhibition of the Sarco-Endoplasmic Reticulum Ca2+ ATPase
(SERCA), the main responsible for ER calcium storage, is able to increase lifespan in Caenorhabditis elegans worms by mechanisms involving mitochondrial metabolism and nutrient-sensitive pathways.
Methods: We have studied here the effects of submaximal SERCA inhibition in a chemical model of Parkinson’s disease (PD) induced in C. elegans worms by treatment with the mitochondrial complex I inhibitor rotenone. For specific SERCA inhibition,we treated worms with RNAi against sca-1, the sole orthologue of SERCA in C. elegans. Results and Discussion: Our results show that rotenone produces alterations in worms that include decreased lifespan, smaller size, reduced fertility, decreased
motility, defecation and pumping rate, increased mitochondrial ROS production, reduced mitochondrial membrane potential and oxygen consumption rate, altered mitochondrial structure, and altered ethanol preference in behavioral studies. Most of these alterations were either fully or partially reversed in worms treated with sca-1 RNAi, suggesting that SERCA inhibition could be a novel pharmacological target in the
prevention or treatment of neurodegeneration.
Palabras Clave
C. elegans, rotenone, Parkinson’s disease, SERCA, lifespan, endoplasmic reticulum, mitochondria, Ca2+ signaling
ISSN
1663-9812
Revisión por pares
SI
Patrocinador
MICINN project BFU2017-83509-R
MICINN project PID 2021-122239OB-I00
MICINN project PID 2021-122239OB-I00
Version del Editor
Idioma
eng
Tipo de versión
info:eu-repo/semantics/publishedVersion
Derechos
openAccess
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