RT info:eu-repo/semantics/article
T1 SERCA inhibition improves lifespan and healthspan in a chemical model of Parkinson disease in Caenorhabditis elegans
A1 Romero-Sanz, Silvia
A1 Caldero Escudero, Elena
A1 Álvarez Illera, María Pilar
A1 Santo Domingo Mayoral, Jaime
A1 Fonteriz García, Rosalba Inés
A1 Montero Zoccola, María Teresa
A1 Álvarez Martín, Javier
K1 C. elegans, rotenone, Parkinson’s disease, SERCA, lifespan, endoplasmic reticulum, mitochondria, Ca2+ signaling
AB 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, decreasedmotility, 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 theprevention or treatment of neurodegeneration.
PB Frontiers
SN 1663-9812
YR 2023
FD 2023
LK https://uvadoc.uva.es/handle/10324/66237
UL https://uvadoc.uva.es/handle/10324/66237
LA eng
NO Frontiers in Pharmacology, May 2023, 14, 1182428
NO Producción Científica
DS UVaDOC
RD 22-may-2024