Increased levels of GM2 ganglioside in fibroblasts from a patient with juvenile Niemann–Pick disease type C

Lysosomal unesterified cholesterol content correlates with liver cell death in murine Niemann-Pick type C disease

“…In both mouse and human with this syndrome, it was shown that there also is tissue accumulation of sphingomyelin and various glycosphingolipids (37,51,52). Furthermore, it was reported that an infant with the NPC mutation and liver disease excreted in its urine several unusual bile acids with a 3b-hydroxy-D 5 structure and an oxo or hydroxyl group at the C-7 position (53).…”

Filipin recognizes both GM1 and cholesterol in GM1 gangliosidosis mouse brain

“…The loss or reduction of ␤ -galactosidase activity results in a failure to cleave the terminal galactosyl residue of ganglioside GM1, leading to excessive central nervous system storage of GM1 and its asialo derivative, GA1 (21)(22)(23)(24)(25). Secondary storage materials are not uncommon in some lipid storage disorders (26)(27)(28)(29). The presence of excess sphingolipid (sphingomyelin or lactosylceramide) alone is suffi cient to induce cholesterol internalization and "trapping" ( 30,31 ).…”

The Niemann-Pick C1 protein in recycling endosomes of presynaptic nerve terminals

“…Additionally, in NPC1-deficient cells, the distribution of cholesterol that has been synthesized endogenously is delayed after its reendocytosis from the plasma membrane (17). The trafficking of gangliosides and other glycosphingolipids is also perturbed (18)(19)(20). In NPC1-deficient brains, cholesterol is sequestered in late endosomes of glia (21) as well as in cell bodies of neurons (22), and impaired anterograde transport of cholesterol in neurons leads to a decrease in the amount of cholesterol in axons (22,23).…”