Intracellular transport and function of cancer- and neurodegenerative disease-related glycosphingolipids

鞘糖脂（GSL）参与癌症和神经退行性疾病的病理生理学。在这项工作中，我研究了神经节苷脂的细胞分布和功能与恶性肿瘤，皮肤癌和尼曼匹克C型（NPC）疾病，神经退行性疾病。结果表明，黑色素瘤相关抗原神经节苷脂GD3在激活参与脂质生物合成的调节因子中起作用，其促进人黑色素瘤细胞膜微区的完整性的脂质生物合成。调节因子的药理学抑制阻止了肿瘤生长。此外，我还研究了与NPC疾病相关的神经节苷脂在NPC细胞中的细胞分布。结果表明，疾病相关的神经节苷脂在溶酶体中积累。几个小分子，促进其从溶酶体到细胞表面的再分布被确定。

Glycosphingolipids (GSLs) are involved in pathophysiology of cancer and neurodegenerative disorders. In this work, I studied cellular distribution and functionalities of gangliosides associated to malanoma, a skin cancer and to Niemann-Pick type C (NPC) disease, a neurodegenerative disorder. The results showed that the melanoma-associated antigen ganglioside GD3 plays a role in the activation of the regulatory factor involved in lipid biosynthesis, which promotes lipid biosynthesis for the integrity of membrane microdomains in human melanoma cells. Pharmacological inhibition of the regulatory factor prevented tumor growth. Also, I studied cellular distribution of gangliosides related to NPC disease in NPC cells. The results showed that disease-associated gangliosides accumulate in the lysosome. Several small-molecules that promote their redistribution from the lysosome to cell surface were identified.