We have determined that the sphingosine kinase/S1P receptor axis has a significant role during neurodegeneration. We used a well-established Sandhoff mouse model of neurodegeneration, which included neuronal apoptosis, inflammation and gliosis. In order to determine if S1P production was important during the neurodegenerative process we deleted the Sphk1 gene in the Sandhoff model. We found a significant improvement in life span and clinical condition of these mice compared with the control Sandhoff mice with a normal Sphk1 gene. These results indicate that Sphk1 expression may have contributed to the neurodegenerative course. Future experiments will address the mechanism of the improved course of the disease.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2012
Total Cost
$668,672
Indirect Cost
City
State
Country
Zip Code
Allende, Maria L; Cook, Emily K; Larman, Bridget C et al. (2018) Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation. J Lipid Res 59:550-563
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