Mitochondrial Na+/Ca2+ exchanger, a new target for neuroprotection in rat hippocampal slices

作者：Nicolau Santos M; Egea Javier; Lopez Manuela G; Garcia Antonio G^*

来源：Biochemical and Biophysical Research Communications, 2010, 400(1): 140-144.

DOI：10.1016/j.bbrc.2010.08.028

• CGP37157
• Mitochondrial sodium/calcium exchanger
• Neurotoxicity
• Neuroprotection
• Veratridine
• Hippocampal slices

We tested here the hypothesis that the pharmacological modulation of the mitochondrial Na+/Ca2+ exchanger (mNCX) could be a new neuroprotective strategy to rescue stressed vulnerable neurons from death. We used rat hippocampal slices incubated with veratridine to cause neuronal death through a mechanism involving Na+ and Ca2+ overload. CGP37157 (CGP), an inhibitor of the mNCX, rescued veratridine vulnerable neurons from death, showing an EC50 of 5 mu M. This neuroprotection was associated to mitigation of veratridine-elicited overproduction of free radicals and to inhibition of the p38 MAPK-linked apoptotic pathway. These results suggest that the mNCX could become a new target to develop compounds with potential therapeutic neuroprotective actions in neurodegenerative diseases.

• 出版日期2010-9-10