Figure 2.

Scheme summarizing the proposed mechanism for lithium induced neuronal apoptosis (Gomez-Sintes and Lucas, 2010). Prolonged administration of lithium produces inhibition of GSK-3, which promotes entry and accumulation of NFAT into the nucleus. Once in the nucleus, NFAT activates the production of FasL. When FasL is secreted outside the cell binds to Fas receptor present in the membrane of the same cell or cells nearby, which triggers death by apoptosis. When NFAT/Fas signaling is blocked by co-administration of Cyclosporin A or when lithium is administered to Fas-deficient mice (lpr) motor deficits and apoptosis are absent.