Niemann-Pick disease type C (NP-C) is an autosomal recessive neurovisceral lipid storage disorder biochemically characterized by a defect in intracellular transport of low-density lipoprotein (LDL)-derived cholesterol from the lysosome to other cellular sites. We have found substantial accumulation of G
M2 ganglioside in NP-C fibroblasts. The intracellular distribution of G
M2 ganglioside was similar to that of cholesterol detected by filipin staining, indicating that the accumulation of G
M2 ganglioside is mainly lysosomal. The incorporation of N-acetyl-D-[
3H]mannosamine into gangliosides was also increased in NP-C fibroblasts, especially into the G
M2 and G
M3 fractions. A culture condition which eliminates cholesterol accumulation does not eliminate G
M2 accumulation. It is suggested that the accumulation of G
M2 ganglioside together with the accumulation of cholesterol is a unique abnormality in NP-C fibroblasts and that the defect in NP-C may involve intracellular transport of both cholesterol and G
M2 ganglioside.
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