title: Mitochondrial Na+/Ca2+ exchanger, a new target for neuroprotection in rat hippocampal slices.
abstract: We tested here the hypothesis that the pharmacological modulation of the mitochondrial Na(+)/Ca(2+) 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 Ca(2+) overload. CGP37157 (CGP), an inhibitor of the mNCX, rescued veratridine vulnerable neurons from death, showing an EC(50) of 5 μM. 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.
authors: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain.
authors: Santos M
authors: SM
authors: Nicolau
authors: Javier
authors: J
authors: Egea
authors: Manuela G
authors: MG
authors: López
authors: Antonio G
authors: AG
authors: García
mesh_terms: D000818:Animals; D002998:Clonazepam / Q000031:analogs & derivatives* / Q000494:pharmacology; D019610:Cytoprotection; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013841:Thiazepines / Q000494:pharmacology*; D014701:Veratridine / Q000633:toxicity
chemical_list: D018696:Neuroprotective Agents; D019831:Sodium-Calcium Exchanger; D013841:Thiazepines; D002998:Clonazepam; D014701:Veratridine; C079032:CGP 37157