In addition to its role in NPD, over the past two decades, the importance of sphingolipids, and ASM in particular, in normal physiology and the pathophysiology of numerous common diseases also has become known.
The Niemann-Pick disease group is now divided into two distinct entities: (1) acid sphingomyelinase-deficient Niemann-Pick disease (ASM-deficient NPD) resulting from mutations in the SMPD1 gene and encompassing type A and type B as well as intermediate forms; (2) Niemann-Pick disease type C (NP-C) including also type D, resulting from mutations in either the NPC1 or the NPC2 gene.
Analysis of the sphingomyelin phosphodiesterase 1 gene (SMPD1) in Turkish Niemann-Pick disease patients: mutation profile and description of a novel mutation.
Because ASMase-knock-out mice models NPD and our previous findings revealed that ASMase activates cathepsins B/D (CtsB/D), our aim was to investigate the expression and processing of CtsB/D in hepatic stellate cells (HSCs) from ASMase-null mice and their role in liver fibrosis.
The objective of this study is to characterize the clinical features of patients with ASM deficiency in the Netherlands and Belgium with focus on the natural disease course of NPD-B patients.
We present a case of a 9-month infant with clinical manifestations intermediate between types A and B NPD and genetically illustrating a novel R542X mutation in the exon 6 of SMPD1.
This review will focus on the role of ASM in membrane biology, with a specific emphasis on what a rare genetic disorder (NPD) has taught us about more common events.
Pulmonary delivery of recombinant acid sphingomyelinase improves clearance of lysosomal sphingomyelin from the lungs of a murine model of Niemann-Pick disease.
Enzymatic dysfunction of acid sphingomyelinase results in Niemann-Pick disease, a lysosomal storage disorder characterized at the cellular level by accumulation of sphingomyelin within the endo-lysosomal compartment.
We further developed a computer assisted, three-dimensional model of human ASM based on homologies to known proteins, and used this model to map each NPD mutation in relation to putative substrate binding, hydrolysis and zinc-binding domains.
We further developed a computer assisted, three-dimensional model of human ASM based on homologies to known proteins, and used this model to map each NPD mutation in relation to putative substrate binding, hydrolysis and zinc-binding domains.
The initial observations implicating ASM in this process have come from studies using cells from patients with NPD or from ASM knockout (ASMKO) mice, where the genetic deficiency of this enzymatic activity has been shown to protect these cells and animals from stress-induced and developmental apoptosis.
Niemann-Pick disease (NPD) is caused by the loss of acid sphingomyelinase (ASM) activity, which results in widespread accumulation of undegraded lipids in cells of the viscera and CNS.
Niemann-Pick disease (NPD), an autosomal recessive disorder resulting from mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene, is subdivided into the acute, lethal neuronopathic type A, and the chronic visceral type B, explained by the different residual activity levels of acid sphingomyelinase (ASMase).
These data thus demonstrate, for the first time, imprinting at the SMPD1 gene and reveal the influence of this epigenetic modification on the presentation of ASM-deficient NPD.