| Literature DB >> 25008046 |
Alejandro Romero1, Javier Egea, Gema C González-Muñoz, Ma Dolores Martín de Saavedra, Laura del Barrio, María Isabel Rodríguez-Franco, Santiago Conde, Manuela G López, Mercedes Villarroya, Cristóbal de los Ríos.
Abstract
The 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 Ca(2+) 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.Entities:
Keywords: Alzheimer’s disease; Dibenzothiadiazepine; amyloid beta; neurodegenerative diseases; neurofibrillary tangles; neuroprotective drugs; oxidative stress
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Year: 2014 PMID： 25008046 DOI： 10.1021/cn500131t
Source DB: PubMed Journal: ACS Chem Neurosci ISSN： 1948-7193 Impact factor: 4.418