RT Journal Article
T1 Melatonin Reduces NLRP3 Inflammasome Activation by Increasing α7 nAChR-Mediated Autophagic Flux.
A1 Farré-Alins, Víctor
A1 Narros-Fernández, Paloma
A1 Palomino-Antolín, Alejandra
A1 Decouty-Pérez, Céline
A1 Lopez-Rodriguez, Ana Belen
A1 Parada, Esther
A1 Muñoz-Montero, Alicia
A1 Gómez-Rangel, Vanessa
A1 López-Muñoz, Francisco
A1 Ramos Alonso, Eva
A1 González-Rodríguez, Águeda
A1 Gandía, Luis
A1 Romero Martínez, Manuel Alejandro
A1 Egea, Javier
AB Microglia controls the immune system response in the brain. Specifically, the activation and dysregulation of the NLRP3 inflammasome is responsible for the initiation of the inflammatory process through IL-1β and IL-18 release. In this work, we have focused on studying the effect of melatonin on the regulation of the NLRP3 inflammasome through α7 nicotinic receptor (nAChR) and its relationship with autophagy. For this purpose, we have used pharmacological and genetic approaches in lipopolysaccharide (LPS)-induced inflammation models in both in vitro and in vivo models. In the BV2 cell line, LPS inhibited autophagy, which increased NLRP3 protein levels. However, melatonin promoted an increase in the autophagic flux. Treatment of glial cultures from wild-type (WT) mice with LPS followed by extracellular adenosine triphosphate (ATP) produced the release of IL-1β, which was reversed by melatonin pretreatment. In cultures from α7 nAChR knock-out (KO) mice, melatonin did not reduce IL-1β release. Furthermore, melatonin decreased the expression of inflammasome components and reactive oxygen species (ROS) induced by LPS; co-incubation of melatonin with α-bungarotoxin (α-bgt) or luzindole abolished the anti-inflammatory and antioxidant effects. In vivo, melatonin reverted LPS-induced cognitive decline, reduced NLRP3 levels and promoted autophagic flux in the hippocampi of WT mice, whereas in α7 nAChR KO mice melatonin effect was not observed. These results suggest that melatonin may modulate the complex interplay between α7 nAChR and autophagy signaling.
PB MDPI
YR 2020
FD 2020
LK https://hdl.handle.net/20.500.14352/120413
UL https://hdl.handle.net/20.500.14352/120413
LA eng
NO Farré-Alins, V., Narros-Fernández, P., Palomino-Antolín, A., Decouty-Pérez, C., Lopez-Rodriguez, A. B., Parada, E., Muñoz-Montero, A., Gómez-Rangel, V., López-Muñoz, F., Ramos, E., González-Rodríguez, Á., Gandía, L., Romero, A., & Egea, J. (2020). Melatonin reduces NLRP3 inflammasome activation by increasing α7 nAChR-mediated autophagic flux. Antioxidants, 9(12), 1-18. https://doi.org/10.3390/ANTIOX9121299
NO Conceptualization, J.E., E.P, V.F.-A., Á.G.-R., L.G. and A.R.; methodology, V.F.-A., P.N.-F.and J.E.; validation, V.F.-A. and J.E.; formal analysis, V.F.-A., A.P.-A. and A.B.L.-R.; investigation, V.F.-A., P.N.-F.,A.P.-A., C.D.-P., E.P., A.M.-M. and V.G.-R.; resources, J.E., L.G. and Á.G.-R.; data curation, V.F.-A. and J.E.;writing—original draft preparation, V.F.-A. and J.E.; writing—review and editing, all authors; visualization, V.F.-A.and J.E.; supervision, J.E., A.R., E.R. and L.G.; project administration, J.E.; funding acquisition, J.E., F.L.-M. andA.R. All authors have read and agreed to the published version of the manuscript.
NO Instituto de Salud Carlos III
NO Universidad Camilo José Cela
DS Docta Complutense
RD 26 jul 2025