• defects
  • Before the molecular defects were described, the terms "Niemann-Pick type I" and "Niemann-Pick type II" were proposed to separate the high- and low-sphingomyelin forms of the disease in the early 1980s. (wikipedia.org)
  • Immune defects, such as chronic neutropenia or lymphocyte impairment, are described in some inherited metabolic diseases (glycogenosis Ib and hereditary orotic aciduria), and may explain the development of marked susceptibility to airway infections [ 13 , 14 ]. (ersjournals.com)
  • lipids
  • In addition, thymocytes and splenocytes from NPC2-deficient mice were poor presenters of endogenous and exogenous lipids to CD1d-restricted Vα14 hybridoma cells. (rupress.org)
  • Importantly, we determined that similar to saposins, recombinant NPC2 was able to unload lipids from and load lipids into CD1d. (rupress.org)
  • phenotype
  • The immunological phenotype of NPC2-deficient mice was limited to an impaired thymic selection of Vα14 natural killer T cells (NKT cells) and a subsequent reduction of NKT cells in the periphery. (rupress.org)
  • These observations strongly suggested that the phenotype observed in NPC2-deficient animals was directly linked to the efficiency of the loading of iGb3 into CD1d molecules expressed by thymocytes. (rupress.org)
  • mice
  • Analyses of lysosome-enriched subcellular fractions from brain and liver revealed similar decreases in buoyant densities of lysosomes from NPC1 or NPC2 deficient mice compared to controls. (jove.com)
  • In the other study, mice that were heterozygous for NPC1 were shown to be protected from lethal challenge with mouse adapted Ebola virus. (wikipedia.org)
  • diagnosis
  • All individuals between the ages of 2 years and 99 with an established diagnosis of Niemann-Pick Disease, Type C (biochemical or molecular) will be considered for this study. (clinicaltrials.gov)
  • Due to the complexity of diagnosis and the availability of an approved therapy in the EU, improved detection of NP-C may have a huge impact on future disease management. (nih.gov)
  • lysosome
  • Moreover, the knowledge of the molecules and processes that take place in the lysosome will shed light on common features of lysosomal storage disorders, on the mechanisms of infection of some viruses like Ebola and on Parkinson's disease, Alzheimer's and inflammatory conditions in which the lysosome is involved. (royalsociety.org)
  • Fabry
  • We present our experience screening newborns in North East Italy to identify neonates with Mucopolysaccharidosis type I (MPS I) and Pompe, Fabry, and Gaucher diseases. (readbyqxmd.com)
  • enzyme
  • However, the development and success of the first commercial biologic therapy for an LSD - enzyme replacement therapy for type 1 Gaucher disease - coupled with regulatory incentives rapidly catalysed commercial interest in therapeutically targeting LSDs. (readbyqxmd.com)
  • Markers
  • Specifically, this study will examine and characterize the longitudinal progression of neurocognitive symptoms of NPC with the goal of identifying early markers of disease progression that may be utilized in later trials to evaluate treatment efficacy. (clinicaltrials.gov)
  • progression
  • Non-coding RNAs (ncRNAs) are a functional class of RNA involved in the regulation of several cellular processes which may modulate disease onset, progression, and prognosis. (frontiersin.org)
  • Ebola
  • In one of the original studies, a small molecule was shown to inhibit Ebola virus infection by preventing the virus glycoprotein from binding to NPC1. (wikipedia.org)
  • mechanism
  • This transfer activity was associated with a dimeric form of NPC2, suggesting a unique mechanism of glycosphingolipid transfer by NPC2. (rupress.org)
  • dysfunctional
  • This disease involves dysfunctional metabolism of sphingolipids, which are fats found in cell membranes, so it is a kind of sphingolipidosis. (wikipedia.org)
  • Currently, the precise function of NPC1 is unknown, but when it is dysfunctional a fatty molecule called sphingosine accumulates in lysosomes. (royalsociety.org)
  • obesity
  • NPC1, in addition to FTO, MC4R, and PTER has recently been shown to be a new risk loci for early-onset and morbid adult obesity in European populations. (blogspot.com)
  • A genome-wide association study identified NPC1 mutations as a risk factor in childhood obesity and adult morbid obesity, and 1,416 age-matched normal weight controls. (wikipedia.org)
  • Study
  • This study will contribute to the understanding of the basis of NPC disease, which could open new avenues for alternative and more effective treatments for this disorder. (royalsociety.org)
  • A later study confirmed the findings that NPC1 is a critical filovirus receptor that mediates infection by binding directly to the viral envelope glycoprotein and that the second lysosomal domain of NPC1 mediates this binding. (wikipedia.org)
  • similar
  • Similar to saposin B, NPC2 dimers were able to load isoglobotrihexosylceramide (iGb3), the natural selecting ligand of NKT cells in the thymus, into CD1d. (rupress.org)
  • The same studies described similar results with Marburg virus, another filovirus, showing that it too needs NPC1 to enter cells. (wikipedia.org)