RT Journal Article
T1 Neuroprotective mechanism of the novel melatonin derivative Neu-P11 in brain ischemia related models
A1 Buendia Abaitua, Izaskun
A1 Gómez Rangel, Vanessa
A1 Gónzalez Lafuente, Laura
A1 Parada Pérez, Esther
A1 León Martínez, Rafael
A1 Gameiro Ros, Isabel Marina
A1 Michalska Dziama, Patrycja
A1 Laudon, Moshe
A1 Egea Máiquez, Francisco Javier
A1 García López, Manuela
AB Stopping the ischemic cascade by targeting its components is a potential strategy for acute ischemic stroke treatment. During ischemia and especially over reperfusion, oxidative stress plays a major role in causing neuronal cell death. Melatonin has been previously reported to provide neuroprotective effects in in vivo models of stroke by a mechanism that implicates melatonin receptors. In this context, this study was planned to test the potential neuroprotective effects of the novel melatonin MT1/MT2 receptor agonist, Neu-P11, against brain ischemia in in vitro and in vivo models, and to elucidate its underlying mechanism of action. Neu-P11 proved to be a good antioxidant, to protect against glutamate-induced excitotoxicity and oxygen and glucose deprivation in hippocampal slices, and to reduce infarct volume in an in vivo stroke model. Regarding its mechanism of action, the protective effect of Neu-P11 was reverted by luzindole (melatonin receptor antagonist), AG490 (JAK2 inhibitor), LY294002 (PI3/AKT inhibitor) and PD98059 (MEK/ERK1/2 inhibitor). In conclusion, Neu-P11 affords neuroprotection against brain ischemia in in vitro and in vivo models by activating a pro-survival signaling pathway that involves melatonin receptors, JAK/STAT, PI3K/Akt and MEK/ERK1/2.
PB Science Direct
YR 2015
FD 2015-12-01
LK https://hdl.handle.net/20.500.14352/96082
UL https://hdl.handle.net/20.500.14352/96082
LA eng
NO Buendia, Izaskun, et al. «Neuroprotective Mechanism of the Novel Melatonin Derivative Neu-P11 in Brain Ischemia Related Models». Neuropharmacology, vol. 99, diciembre de 2015, pp. 187-95. DOI.org (Crossref), https://doi.org/10.1016/j.neuropharm.2015.07.014.
NO Ministerio de Economía, Comercio y Empresa (España)
NO Universidad Autónoma de Madrid
NO Instituto de Salud Carlos III
NO European Commission
NO Marie Curie Actions FP7
DS Docta Complutense
RD 12 abr 2025