Figure 1: Model for acute neurodegeneration in GSL storage disease
In this model, the storage of GSLs 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 GSLs leads to their activation and the recruitment of additional microglial precursors from blood. The large expansion of the activated microglial population produces high levels of neurotoxic mediators, which provide an additional insult to the neurons already stressed by GSL storage, resulting in widespread neuronal apoptosis.
For details, see Wada R, Tifft CJ, Proia RL. Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation. Proceedings of the National Academy of Sciences of the United States of America 97(20):10954-10959, 2000. [Entrez]
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