ITH33/IQ-M9.21 provides neuroprotection in a novel ALS model based on TDP-43 and Na+/Ca2' overload induced by VTD

被引:2
作者
Mouhid Al-achbili, Lamia [1 ,2 ]
Moreno-Ortega, Ana J. [1 ,2 ,3 ]
Matias-Guiu, Jorge [4 ,5 ]
Cano-Abad, Maria F. [1 ,2 ,3 ]
Ruiz-Nuno, Ana [1 ,3 ]
机构
[1] Univ Autonoma Madrid, Fac Med, Inst Fdn Teofilo Hernando, Madrid, Spain
[2] Univ Autonoma Madrid, Fac Med, Dept Farmacol & Terapeut, Madrid, Spain
[3] Univ Autonoma Madrid, Hosp Univ Princesa, Inst Invest Sanitaria, Serv Farmacol Clin, Madrid, Spain
[4] Univ Complutense Madrid, Hosp Clin San Carlos, Serv Neurol, Madrid, Spain
[5] Univ Complutense Madrid, Hosp Clin San Carlos, Inst Neurociencias, Madrid, Spain
关键词
NSC-34; cells; Veratridine; Ca2+; Apoptosis; TDP-43; Amyotrophic lateral sclerosis; AMYOTROPHIC-LATERAL-SCLEROSIS; CYTOSOLIC CA2+ OSCILLATIONS; UNFOLDED PROTEIN RESPONSE; BOVINE CHROMAFFIN CELLS; DNA-BINDING PROTEIN-43; IN-VITRO; ENDOPLASMIC-RETICULUM; VERATRIDINE; CALCIUM; DEATH;
D O I
10.1016/j.neulet.2016.09.009
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Therapeutic options for amyotrophic lateral sclerosis (ALS) are scarce and controversial. Although the aetiology of neuronal vulnerability is unknown, growing evidence supports a complex network in which multiple toxicity pathways, rather than a single mechanism, are involved in the pathogenesis of ALS. However, most cellular models only explain single pathogenic mechanisms. The present study proposes the two main cytotoxic mechanisms: (1) veratridine (VTD), which induced Na+ and Ca2+ overload; and (2) the TARD DNA-binding protein 43 (TDP-43) in NSC-34 cell line as an in vitro model of ALS. The study was carried out by MTT as an indirect measurement of cell viability and by flow cytometry to determine cell death stages. The impact of Ca2+ overload combined with TDP-43 overexpression increased early apoptosis of NSC-34 cells. Furthermore, we found that ITH33/IQM9.21 (ITH33) exerted a neuroprotective effect in this model by reducing activation of the apoptotic pathway. Therefore, treatment with VTD in TDP-43 overexpressing NSC-34 cells is a good in vitro ALS model that makes it possible to test new neuroprotective compounds such as ITH33. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
引用
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页码:28 / 32
页数:5
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