Figure 5.

Model for acute neurodegeneration in G_M2 gangliosidoses. In this model, storage of G_M2 ganglioside and related glycolipids causes primary neuronal damage. Microglia recognize damaged and dying neurons and remove them by phagocytosis. The inability of the enzyme-deficient microglia to catabolize endocytosed glycolipid leads to their activation and the recruitment of additional microglial precursors from blood. The large expansion of the activated microglial population produces neurotoxic mediators, which provides an additional insult to the neurons already stressed by glycolipid storage, resulting in widespread neuronal apoptosis. BMT may disrupt this pathway through the introduction of normal microglia into the CNS. These normal microglia can effectively remove the neurons damaged by storage and, thus, temporarily suppress the recruitment and expansion of the activated microglial population.