| First Author | Lee H | Year | 2014 |
| Journal | Mol Cells | Volume | 37 |
| Issue | 2 | Pages | 161-71 |
| PubMed ID | 24599001 | Mgi Jnum | J:309876 |
| Mgi Id | MGI:6708274 | Doi | 10.14348/molcells.2014.2347 |
| Citation | Lee H, et al. (2014) Inhibition of GM3 synthase attenuates neuropathology of Niemann-Pick disease Type C. by affecting sphingolipid metabolism. Mol Cells 37(2):161-71 |
| abstractText | In several lysosomal storage disorders, including Niemann-Pick disease Type C (NP-C), sphingolipids, including glycosphingolipids, particularly gangliosides, are the predominant storage materials in the brain, raising the possibility that accumulation of these lipids may be involved in the NP-C neurodegenerative process. However, correlation of these accumulations and NP-C neuropathology has not been fully characterized. Here we derived NP-C mice with complete and partial deletion of the Siat9 (encoding GM3 synthase) gene in order to investigate the role of ganglioside in NP-C pathogenesis. According to our results, NPC mice with homozygotic deletion of GM3 synthase exhibited an enhanced neuropathological phenotype and died significantly earlier than NP-C mice. Notably, in contrast to complete depletion, NP-C mice with partial deletion of the GM3 synthase gene showed ameliorated NP-C neuropathology, including motor disability, demyelination, and abnormal accumulation of cholesterol and sphingolipids. These findings indicate the crucial role of GM3 synthesis in the NP-C phenotype and progression of CNS pathologic abnormality, suggesting that well-controlled inhibition of GM3 synthesis could be used as a therapeutic strategy. |
