Extracellular uridine diphosphate-mediated microglial inflammation in a mouse model of Sandhoff disease

Sandhoff disease (SD) is an inherited lysosomal storage disease caused by a β-hexosaminidase deficiency involving excessive accumulation of undegraded substrates, including GM2 ganglioside, which leads to neurological symptoms, such as mental retardation, spasms and quadriplegia. Macrophage inflammatory protein-1α (MIP-1α) is a crucial factor for microglia-mediated neuroinflammation in the onset or progression of SD. However, there was no therapeutic approach to control the abnormal production of MIP-1α in the brain of SD, and the mechanisms underlying the MIP-1α production by microglia, especially the transmitter-mediated production, remains unclear.