Lysosomal storage diseases (LSDs) often manifest with severe systemic and central nervous system (CNS) symptoms. The existing treatment options are limited and have no or only modest efficacy against neurological manifestations of disease. We demonstrate that recombinant human heat shock protein 70 (HSP70) improves the binding of several sphingolipid-degrading enzymes to their essential cofacto...

We have generated an acid sphingomyelinase (aSMase)-deficient mouse line by gene targeting. This novel strain of mutant mouse mimics the lethal, neurovisceral form of the human sphingomyelin storage disease, known as Niemann-Pick disease. Homozygous mice accumulate sphingomyelin extensively in the reticuloendothelial system of liver, spleen, bone marrow, and lung, and in the brain. Most strikin...

Niemann-Pick type C1 disease is an autosomal-recessive lysosomal storage disorder. Loss of function of the npc1 gene leads to abnormal accumulation of free cholesterol and sphingolipids within the late endosomal and lysosomal compartments resulting in progressive neurodegeneration and dysmyelination. Here, we show that oligodendroglial cells secrete cholesterol by exosomes when challenged with ...