ITH12410/SC058: A New Neuroprotective Compound with
Potential in the Treatment of Alzheimer’s Disease
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 Ríos
10.1021/cn500131t.s001
https://acs.figshare.com/articles/journal_contribution/ITH12410_SC058_A_New_Neuroprotective_Compound_with_Potential_in_the_Treatment_of_Alzheimer_s_Disease/2254231
The
neuroprotective profile of the dibenzothiadiazepine ITH12410/SC058
(2-chloro-5,6-dihydro-5,6-diacetyldibenzo[<i>b</i>,<i>f</i>][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, H<sub>2</sub>O<sub>2</sub> 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<sup>2+</sup> 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.
2014-09-17 00:00:00
5Y
neurofibrillary tangle formation
neuroprotective
H 2O exposure
neurodegenerative diseases
amyloid beta peptide
ITH
phosphoprotein phosphatase 2
rat hippocampal slices