FIGURE 2.

Intrinsic mechanisms regulating preOL survival and integration. After terminal differentiation from OPCs, preOLs must pass through a survival checkpoint during which a majority are lost. At this survival checkpoint a complex web of intracellular signaling mechanisms work to either drive preOL death or to encourage survival and integration. (A) A schematic representation of the survival checkpoint. PreOLs can either be driven toward cell death (red) or survival and integration (blue). (B) Intrinsic signaling pathways in preOLs. Pathways in blue promote the survival and integration of preOLs. The metabolite Taurine leads to increased serine pools that are available for lipid synthesis pathways (Beyer et al., 2018). The metabolite folate promotes survival by activating AMPKα phosphorylation (Weng et al., 2017). Gsta4 regulates oxidative stress via extracellular transport of 4-HNE (Carlstrom et al., 2020). Pathways in red promote cell death in preOLs. Increased 4-HNE load leads to increased Fas-Casp8-Bid signaling (Carlstrom et al., 2020). Hypoxic conditions result in increased HIF1/2a (Yuen et al., 2014). mTOR deletion leads to increased expression of the oligodendrocyte maturation inhibiting promotor ID2 (Ornelas et al., 2020). Reduction of Tsc1/2 results in hyperactive mTOR, increased translation and ER stress, and increased Fas-JNK signaling (Jiang et al., 2016). TFEB promotes ER stress and increases the expression of PUMA which subsequently leads to increased Bax/Bak activity (Sun et al., 2018).