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
K1 rotenone
K1 Parkinson’s disease
K1 SERCA
K1 lifespan
K1 endoplasmic reticulum
K1 mitochondria
K1 Ca2+ signaling
K1 2411.99 Otras
K1 3209.99 Otras
AB Introduction: The high prevalence of neurodegenerative diseases in ourpopulation and the lack of effective treatments encourage the search for newtherapeutic targets for these pathologies. We have recently described thatsubmaximal inhibition of the Sarco-Endoplasmic Reticulum Ca2+ ATPase(SERCA), the main responsible for ER calcium storage, is able to increaselifespan in Caenorhabditis elegans worms by mechanisms involvingmitochondrial metabolism and nutrient-sensitive pathways.Methods: We have studied here the effects of submaximal SERCA inhibition in achemicalmodel of Parkinson’s disease (PD) induced in C. elegansworms by treatmentwith themitochondrial complex I inhibitor rotenone. For specific SERCA inhibition,wetreated worms with RNAi against sca-1, the sole orthologue of SERCA in C. elegans.Results and Discussion: Our results show that rotenone produces alterations inworms 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, alteredmitochondrial structure, and altered ethanol preference in behavioral studies. Most ofthese alterations were either fully or partially reversed in worms treated with sca-1RNAi, 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/10324/66076
UL https://uvadoc.uva.es/handle/10324/66076
LA eng
NO Frontiers in Pharmacology, 2023, vol. 14, 1182428
NO Producción Científica
DS UVaDOC
RD 27-dic-2024