Journal
ACS CHEMICAL NEUROSCIENCE
Volume 5, Issue 9, Pages 770-775Publisher
AMER CHEMICAL SOC
DOI: 10.1021/cn500131t
Keywords
Dibenzothiadiazepine; neurodegenerative diseases; oxidative stress; Alzheimer's disease; amyloid beta; neurofibrillary tangles; neuroprotective drugs
Funding
- Spanish Institutions
- Proyectos de Investigacion en Salud (IS Carlos III) [PI13/00789]
- Spanish Ministry of Science and Innovation [SAF2009-12150]
- Spanish Ministry of Economy and Competitiveness [SAF2012-31035]
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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 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.
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