Protection against neurodegeneration with low-dose methylene blue and near-infrared light

Neurons are metabolically protected against degeneration using low-level methylene blue and near-infrared light interventions. Both of these novel interventions act by a cellular mechanism involving enhancement of the electron transport chain in mitochondria, which promotes energy metabolism and neuronal survival (Gonzalez-Lima et al., 2014). Methylene blue preferentially enters neuronal mitochondria after systemic administration, and at low-doses forms an electron cycling redox complex that donates electrons to the mitochondrial electron transport chain. Low-level near-infrared light applied transcranially delivers photons to cortical neurons that are accepted by cytochrome oxidase, which causes increased cell respiration and cerebral blood flow. Breakthrough in vivo studies with these interventions suggest that targeting mitochondrial respiration may be beneficial for protection against different types of neurodegenerative disorders. The purpose of this paper is to provide an update on the cellular mechanisms mediating the neuroprotective effects of low doses of methylene blue and near-infrared light, and to argue that the neurotherapeutic benefits of these two different interventions share the same cellular mechanism of action based on stimulation of mitochondrial respiration. Presented first is the explanation of the biochemical redox action of low-dose methylene as an electron cycler on the mitochondrial electron transport. Presented second is the explanation of the biophysical action of near-infrared light as a photon donor to cytochrome oxidase that also serves to stimulate mitochondrial electron transport. We finish with a comparison of these two interventions and how they share a common cellular mechanism with similar properties such as energy transfer, low-dose hormetic dose-responses, and enhanced capacity for oxidative metabolic energy production, which serve to protect nervous tissue from degeneration.