Mitochondrial uncoupling as a potential therapeutic target in acute central nervous system injury


Address correspondence and reprint requests to William F. Maragos, University of Kentucky Medical Center, Department of Neurology, Health Sciences Research Building, Room 262, Lexington, Kentucky 40536–0305, USA. E-mail:


Mitochondrial dysfunction, resulting from the disruption of calcium homeostasis and the generation of toxic reactive oxygen species, is a central process leading to neuronal injury and death following acute CNS insults. Interventions aimed at preventing disturbances in mitochondrial function have therefore become targets of intense investigation. Mitochondrial uncoupling is a condition in which electron transport is disconnected from the production of ATP. As a consequence, there is a decrease in the mitochondrial membrane potential, which can temporarily decrease calcium influx and attenuate free radical formation. The potential use of pharmacological agents with uncoupling properties may provide a novel therapeutic approach for the treatment of acute neuronal injury.