Olesoxime, E-

Olesoxime interacts with a physiologically relevant target: the mitochondrial permeability transition pore (mPTP). Mitochondria are central mediators of cell death and are implicated in most if not all neurodegenerative diseases regardless of the initiating factor: genetic mutations, excitotoxicity, reactive oxygen species, ischemia, chemical toxicity, etc. Mitochondria play diverse roles in all cells. In neurons, especially near synaptic sites, mitochondria are essential calcium-buffering organelles in areas where membrane excitability leads to large influx of calcium through calcium channels. Mitochondria also produce the ATP necessary for microtubule-based axoplasmic transport and maintaining the activity of ion and nutrient transporters. If a neuron fails to establish or maintain its functional role, mitochondria are responsible for eliminating it by releasing apoptotic factors. Olesoxime, by interacting with protein components of the mPTP, prevents the release of these apoptotic factors and therefore protects the neuron. This mechanism of action may lead to a general neuroprotective activity with utility in other therapeutic indications.