2026-04-14T15:13:28Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/660762025-01-10T13:45:24Zcom_10324_1134com_10324_931com_10324_894com_10324_32522com_10324_952col_10324_1213col_10324_32523

Romero Sanz, Silvia Caldero Escudero, Elena Álvarez Illera, María Pilar Santo Domingo Mayoral, Jaime Fonteriz García, Rosalba Inés Montero Zoccola, María Teresa Álvarez Martín, Javier 2024-02-09T11:30:20Z 2024-02-09T11:30:20Z 2023 Frontiers in Pharmacology, 2023, vol. 14, 1182428 1663-9812 https://uvadoc.uva.es/handle/10324/66076 10.3389/fphar.2023.1182428 Frontiers in Pharmacology 14 1663-9812 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 chemicalmodel of Parkinson’s disease (PD) induced in C. elegansworms by treatment with themitochondrial 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. eng info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/4.0/ © 2023 The Authors Attribution 4.0 Internacional SERCA inhibition improves lifespan and healthspan in a chemical model of Parkinson disease in Caenorhabditis elegans info:eu-repo/semantics/article