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ITH12410/SC058: A New Neuroprotective Compound with Potential in the Treatment of Alzheimer's Disease

AuthorsRomero, Alejandro ; Egea, Javier; González-Muñoz, Gema C. ; Martín de Saavedra, María Dolores; Barrio, Laura del; Rodríguez-Franco, María Isabel ; Conde, Santiago ; Lopez, Manuela G.; Villarroya, Mercedes; Ríos, Cristóbal de los
Issue Date2014
PublisherAmerican Chemical Society
CitationACS Chemical Neuroscience 5: 770-775 (2014)
AbstractThe 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.
Identifiersdoi: 10.1021/cn500131t
issn: 1948-7193
e-issn: 1948-7193
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