Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2300 RA, Leiden, The Netherlands.
Essays Biochem. 2020 Sep 23;64(3):565-578. doi: 10.1042/EBC20190090.
Lyso-glycosphingolipids are generated in excess in glycosphingolipid storage disorders. In the course of these pathologies glycosylated sphingolipid species accumulate within lysosomes due to flaws in the respective lipid degrading machinery. Deacylation of accumulating glycosphingolipids drives the formation of lyso-glycosphingolipids. In lysosomal storage diseases such as Gaucher Disease, Fabry Disease, Krabbe disease, GM1 -and GM2 gangliosidosis, Niemann Pick type C and Metachromatic leukodystrophy massive intra-lysosomal glycosphingolipid accumulation occurs. The lysosomal enzyme acid ceramidase generates the deacylated lyso-glycosphingolipid species. This review discusses how the various lyso-glycosphingolipids are synthesized, how they may contribute to abnormal immunity in glycosphingolipid storing lysosomal diseases and what therapeutic opportunities exist.
溶酶体糖脂在糖脂贮积症中过量产生。在这些病理过程中，由于脂质降解机制的缺陷，糖鞘脂在溶酶体中积累。积累的糖脂的去酰化作用驱动溶酶体糖脂的形成。在溶酶体贮积病中，如戈谢病、法布雷病、Krabbe 病、GM1-和 GM2 神经节苷脂贮积症、尼曼-皮克 C 型病和黏脂贮积症，大量的溶酶体内糖脂积累发生。溶酶体酶酸性神经酰胺酶产生去酰化的溶酶体糖脂。本综述讨论了各种溶酶体糖脂的合成方式，它们如何导致糖脂贮积溶酶体疾病中的异常免疫，以及存在哪些治疗机会。
