Introduction: The recent failure of the clinical trial of ninocycline outlines if the mechanism of development of the death neuronal in the sporadic amyotrophic lateral sclerosis (SALS) is different to that happens in models of transgenic mice with human mutations related with SOD (TgALS).
Method: Differences on profile and intensity exist among the oxidative stress mechanisms between TgALS and SALS. Whereas the origin of apoptosis pathway in TgALS comes from the mithocondria and drives to caspase 9 with previous Bid and citocrome C discharge, in SALS, if apoptosis exists, that could proceed through activation of FAS pathway by means of cathepsin B, or alpha-TNF, for microglía activation or from cell cytosol. In FAS pathway, TNF-alpha acts receptor ligands what drives to caspase 8 activation, although cathepsine B could act directly. Considering that the minocyicline decreases Citocrome discharge, reducing executors caspases expression proceeding from intrinsic pathway, is justified its effectiveness in TgALS, but could not be explained if apoptosis in SALS was developed primarily on FAS pathway.
Conclusions: Better knowledge of how cellular death occurs in SALS, could allow to suggest therapeutic options, and could permit to discriminate drugs that, showing effectiveness in TgALS, could not be beneficials in SALS.