Fig. 1From: Neuroprotective therapies for multiple sclerosis and other demyelinating diseasesProposed targets for neuroprotective therapies. The pathways involved in neuroprotection include 1) Active axonal degeneration pathway activation (mediated by depletion of NAD levels by NMNAT2, PHR1 and Sarm1 activation); 2) trophic factor signaling (PI3K, MAPKK, NFkB); 3) oxidative stress (induced by inflammatory cells and mitochondria dysfunction); 4) energy depletion (due to mitochondria impairment and increased demand from Ca channels); 5) axonal transport blockade (failing to deliver mitochondria, signaling and molecular complexes to soma, nodes of Ranvier or synpasis); 6) ionic imbalance (due to ion channel redistribution and changes in activity, leading to increase of intracellular calcium); 7) Excitotoxicity (mediated by excess of glutamate signaling through the NMDA receptors); 8) remyelination (from OPC repopulation of demyelinated areas to myelination of denuded axons by mature oligodendrocytes (OG), which provide metabolic support to the axon (NAA or PC); 9) protective effects of astrocytes (providing trophic factors such as IGF-1 or BDNF, metabolic substrates such as lactate, or pro-survival signals such as CD200-CD200L) and M2 microglia (with scavenger and tissue healing activity)Back to article page