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

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• 作者：Alejandro Romero ; Javier Egea ; Gema C. Gonz谩lez-Mu帽oz ; M^a Dolores Mart谋虂n de Saavedra ; Laura del Barrio ; Mar铆a Isabel Rodr铆guez-Franco ; Santiago Conde ; Manuela G. L贸pez ; Mercedes Villarroya ; Crist贸bal de los R铆os
• 刊名：ACS Chemical Neuroscience
• 出版年：2014
• 出版时间：September 17, 2014
• 年：2014
• 卷：5
• 期：9
• 页码：770-775
• 全文大小：225K
• ISSN：1948-7193

文摘

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.

Keywords:

Dibenzothiadiazepine; neurodegenerative diseases; oxidative stress; Alzheimer鈥檚 disease; amyloid beta; neurofibrillary tangles; neuroprotective drugs