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ITH12410/SC058: A New Neuroprotective Compound with Potential in the Treatment of Alzheimer’s Disease
journal contribution
posted on 2014-09-17, 00:00 authored by Alejandro Romero, Javier Egea, Gema C. González-Muñoz, M Martı́n de
Saavedra, Laura del Barrio, María Isabel Rodríguez-Franco, Santiago Conde, Manuela G. López, Mercedes Villarroya, Cristóbal de los RíosThe
neuroprotective profile of the dibenzothiadiazepine ITH12410/SC058
(2-chloro-5,6-dihydro-5,6-diacetyldibenzo[b,f][1,4,5]thiadiazepine) against several neurotoxicity models
related to neurodegenerative diseases is herein described. ITH12410/SC058
protected SH-SY5Y cells against the loss of cell viability elicited
by amyloid beta peptide and okadaic acid, a selective inhibitor of
phosphoprotein phosphatase 2A that induces neurofibrillary tangle
formation. Furthermore, ITH12410/SC058 is neuroprotective against
several in vitro models of oxidative stress, that is, H2O2 exposure or incubation with rotenone plus oligomycin
A in SH-SY5Y cells, and oxygen and glucose deprivation followed by
reoxygenation in rat hippocampal slices. By contrast, ITH12410/SC058
was unable to significantly protect SH-SY5Y neuroblastoma cells against
the toxicity elicited by Ca2+ overload. Our results confirm
the hypothesis that the dibenzothiadiazepine ITH12410/SC058 features
its neuroprotective actions in a multitarget fashion, and is a promising
drug for the treatment of neurodegenerative diseases.