Cell death in the oligodendrocyte lineage: a molecular perspective of life/death decisions in development and disease

Cell death in the oligodendrocyte lineage occurs during development and in pathological conditions as the result of a balance between opposing molecular signals. This review focuses on the molecular mechanisms of activation of signal transduction pathways affecting life/death decisions in progenitor cells and in mature oligodendrocytes. Loss of trophic support, cytokine receptor activation, and oxidative stress may differentially contribute to the induction of cell death at specific stages of development and to the pathogenesis of demyelinating disorders. The execution of the death program leading to the morphological changes of apoptosis and/or necrosis is then determined by the generation of reactive oxygen species and the level of impairment of mitochondrial function. The final decision of a cell to die or survive is determined by a competition between survival and death signals. Depending on ligand availability, type, and levels of receptor expression and downstream cross-talks between distinct signaling pathways, the cell may activate a death execution program that will be affected by its stage of differentiation and its energetic metabolism.