Acid sphingomyelinase (ASMase, ASM, SMPD1) converts sphingomyelin into ceramide, modulating membrane properties and signal transduction. Inactivating mutations in ASMase cause Niemann-Pick disease, and its inhibition is also beneficial in models of depression and cancer. To gain a better understanding of this critical therapeutic target, we determined crystal structures of mammalian ASMase in v...

Among all inborn errors of metabolism lysosomal storage diseases occupy an important place, because they have a diverse clinical symptoms, manifest at different ages and are disguised as diseases, which makes the diagnosis these quite difficult long-term. Niemann-Pick disease, rare inherited neurodegenerative disease caused by disruption intracellular lipid metabolism, is one such disease. The ...

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Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lipid storage with a wide spectrum of clinical phenotypes. At the cellular level, the disorder is characterized by accumulation of unesterified cholesterol and glycolipids in the lysosomal/late endosomal system. Approximatively 95% of patients have mutations in the NPC1 gene (mapped at 18q11) which encodes a large membran...