Alternative Mitochondrial Electron Transfer as a Novel Strategy for Neuroprotection

摘要: Neuroprotective strategies, including free radical scavengers, ion channel modulators, and anti-inflammatory agents, have been extensively explored in the last 2 decades for treatment of neurological diseases. Unfortunately, none neuroprotectants has proved effective clinical trails. In current study, we demonstrated that methylene blue (MB) functions as an alternative electron carrier, which accepts electrons from NADH transfers them to cytochrome c bypasses complex I/III blockage. A de novo synthesized MB derivative, with redox center disabled by N-acetylation, had no effect on mitochondrial activities. increases cellular oxygen consumption rates reduces anaerobic glycolysis cultured neuronal cells. is protective against various insults vitro at low nanomolar concentrations. Our data indicate a unique mechanism fundamentally different traditional antioxidants. We examined effects two animal models dramatically attenuates behavioral, neurochemical, neuropathological impairment Parkinson disease model. Rotenone caused severe dopamine depletion striatum, was almost completely rescued MB. rotenone I-III inhibition overproduction. induced loss nigral dopaminergic neurons, attenuated addition, significantly reduced cerebral ischemia reperfusion damage transient focal The present study indicates rerouting transfer or similar molecules provides novel strategy neuroprotection both chronic acute diseases involving dysfunction.