• lipids
  • Niemann-Pick diseases are a subgroup of lipid storage disorders called sphingolipidoses in which harmful quantities of fatty substances, or lipids, accumulate in the spleen, liver, lungs, bone marrow, and brain. (wikipedia.org)
  • 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)
  • mice
  • 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)
  • 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)
  • phenotype
  • 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)
  • 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)
  • manifestations
  • This review will describe the most exemplary respiratory manifestations of inherited metabolic diseases in childhood and adulthood. (ersjournals.com)
  • Since airways disease worsens the morbidity of many inherited metabolic disorders, leading to increased hospitalisations, mortality and overall healthcare costs, respiratory manifestations of inherited metabolic diseases need to be carefully recognised and treated. (ersjournals.com)
  • neurodegenerative
  • Niemann-Pick Disease, Type C (NPC) is a rare neurodegenerative disorder with a wide clinical spectrum and variable age of onset. (clinicaltrials.gov)
  • Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease characterized by the selective death of motor neurons. (paperity.org)
  • This rare inherited neurodegenerative disease is caused by a defect in lipid movement within cells and results in cognitive impairment, ataxia, dementia and premature death, most often in childhood. (royalsociety.org)
  • efficacy
  • 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)
  • 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)
  • 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)
  • receptor
  • 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)
  • severe
  • Neonates can present with ascites and severe liver disease from infiltration of the liver and/or respiratory failure from infiltration of the lungs. (nih.gov)
  • Niemann-Pick disease (/niːmənˈpɪk/ nee-mən-PIK) is a group of inherited, severe metabolic disorders in which sphingomyelin accumulates in lysosomes in cells. (wikipedia.org)
  • In the terminal stages of Niemann-Pick type C disease, the patient is bedridden, with complete ophthalmoplegia, loss of volitional movement and severe dementia. (wikipedia.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)
  • 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)
  • liver
  • Other infants, without liver or pulmonary disease, have hypotonia and developmental delay. (nih.gov)
  • 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)
  • 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)
  • mechanism
  • This transfer activity was associated with a dimeric form of NPC2, suggesting a unique mechanism of glycosphingolipid transfer by NPC2. (rupress.org)
  • Progressive
  • Several inherited metabolic diseases involve nervous or neuromuscular systems, are usually progressive, and often cause chronic airway aspiration and respiratory infections. (ersjournals.com)
  • function
  • have described similarities between the NPC1 protein and members of the resistance-nodulation-division (RND) family of prokaryotic permeases, suggesting a pumping function for NPC1. (wikipedia.org)