3,351 results match your criteria Niemann-Pick Disease


NPC1-deficient neurons are selectively vulnerable for statin treatment.

Neuropharmacology 2019 Apr 17. Epub 2019 Apr 17.

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin und Berlin Institute of Health; Institut für Integrative Neuroanatomie, Klinische Zell- und Neurobiologie, CC2, Charité, 10117, Berlin, Germany.

Niemann Pick C (NPC) is a fatal hereditary neurovisceral disorder associated with a progressive loss of neurons of unknown mechanism. The disease is caused by mutation in either of two genes, termed npc1 and npc2, accounting for ∼95% and ∼5% of patients, respectively. Recent data suggest a cell-autonomous cause for neuronal cell death. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuropharm.2019.04.012DOI Listing

The complexity of a monogenic neurodegenerative disease: More than two decades of therapeutic driven research into Niemann-Pick type C disease.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 16. Epub 2019 Apr 16.

Department of Biology, Barnard College-Columbia University, New York, NY 10027, United States of America. Electronic address:

Niemann-Pick type C (NP-C) disease is a rare and fatal neurodegenerative disease typified by aberrations in intracellular lipid transport. Cholesterol and other lipids accumulate in the late endosome/lysosome of all diseased cells thereby causing neuronal and visceral atrophy. A cure for NP-C remains elusive despite the extensive molecular advances emanating from the identification of the primary genetic defect in 1997. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbalip.2019.04.002DOI Listing
April 2019
1 Read

Nonglucuronidated Ezetimibe Disrupts CD13- and CD64-Coassembly in Membrane Microdomains and Decreases Cellular Cholesterol Content in Human Monocytes/Macrophages.

Cytometry A 2019 Apr 17. Epub 2019 Apr 17.

Institute for Clinical Chemistry and Laboratory Medicine, University Hospital of Regensburg, 93053 Regensburg, Germany.

Ezetimibe (EZE) and glucuronidated EZE (EZE-Glu) differentially target Niemann-Pick C1-like 1 (NPC1L1) and CD13 (aminopeptidase-N) to inhibit intestinal cholesterol absorption and cholesterol processing in other cells, although the precise molecular mechanisms are not fully elucidated. Cellular effects of EZE, EZE-Glu, and the low-absorbable EZE-analogue S6130 were investigated on human monocyte-derived macrophages upon loading with atherogenic lipoproteins. EZE and S6130, but not EZE-Glu disturbed the colocalization of CD13 and its coreceptor CD64 (Fcγ receptor I) in membrane microdomains, and decreased the presence of both receptors in detergent-resistant membrane fractions. Read More

View Article

Download full-text PDF

Source
https://onlinelibrary.wiley.com/doi/abs/10.1002/cyto.a.23772
Publisher Site
http://dx.doi.org/10.1002/cyto.a.23772DOI Listing
April 2019
1 Read

Gene expression profile in patients with Gaucher disease indicates activation of inflammatory processes.

Sci Rep 2019 Apr 15;9(1):6060. Epub 2019 Apr 15.

Laboratory of Microarray Analysis, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.

Gaucher disease (GD) is a rare inherited metabolic disease caused by pathogenic variants in the GBA1 gene. So far, the pathomechanism of GD was investigated mainly in animal models. In order to delineate the molecular changes in GD cells we analysed gene expression profile in cultured skin fibroblasts from GD patients, control individuals and, additionally, patients with Niemann-Pick type C disease (NPC). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-42584-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465595PMC
April 2019
1 Read
5.078 Impact Factor

Membrane lipids and their degradation compounds control GM2 catabolism at intralysosomal luminal vesicles.

J Lipid Res 2019 Apr 15. Epub 2019 Apr 15.

University Bonn, Germany

The catabolism of ganglioside GM2 is dependent on three gene products. Mutations in any of these genes result in a different type of GM2 gangliosidosis (Tay-Sachs disease, B1 variant, Sandhoff disease and the AB-variant), with GM2 as major lysosomal storage compound. GM2 is also a secondary storage compound in lysosomal storage diseases like Niemann-Pick disease type A, B and C with primary storage of SM and cholesterol, respectively. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1194/jlr.M092551DOI Listing
April 2019
1 Read

Sensitivity, advantages, limitations, and clinical utility of targeted next-generation sequencing panels for the diagnosis of selected lysosomal storage disorders.

Genet Mol Biol 2019 Apr 11. Epub 2019 Apr 11.

Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Lysosomal storage disorders (LSDs) constitute a heterogeneous group of approximately 50 genetic disorders. LSDs diagnosis is challenging due to variability in phenotype penetrance, similar clinical manifestations, and a high allelic heterogeneity. A powerful tool for the diagnosis of the disease could reduce the "diagnostic odyssey" for affected families, leading to an appropriate genetic counseling and a better outcome for current therapies, since enzyme replacement therapies have been approved in Brazil for Gaucher, Fabry, and Pompe diseases, and are under development for Niemann-Pick Type B. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1590/1678-4685-GMB-2018-0092DOI Listing
April 2019
1 Read

Multimodal imaging including optical coherence tomography angiography in patients with type B Niemann-Pick disease.

Int Ophthalmol 2019 Apr 11. Epub 2019 Apr 11.

Department of Pediatrics, Division of Nutrition and Metabolism, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey.

Purpose: To evaluate accumulation patterns of deposits in retinal layers of type B Niemann-Pick patients by multimodal imaging.

Methods: Seven patients with type B Niemann-Pick disease were included in this study. All participants underwent a complete ophthalmologic evaluation, high-resolution digital colour imaging, spectral-domain optical coherence tomography, blue light fundus autofluorescence and optical coherence tomography angiography (OCTA). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10792-019-01102-yDOI Listing
April 2019
1 Read

Sleep disorders in NiemannPick disease type C, beyond cataplexy.

Sleep Med 2019 Feb 19;57:122-127. Epub 2019 Feb 19.

Division of Neurology, Department of Clinical Medicine, Universidade Federal do Ceará, Brazil; Neurology Service, Hospital Geral de Fortaleza, Fortaleza, Ceará, Brazil; Center of Health Sciences, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil. Electronic address:

Purpose: The aim of this study was to clinically characterize sleep disorders in a cohort of Niemann-Pick type C (NPC) patients, correlating these findings with disease features and polysomnographic (PSG) results.

Methods: We evaluated eight consecutive patients with molecular confirmation of NPC followed at the Hospital Geral de Fortaleza. Patients underwent a comprehensive neurological and sleep evaluation. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sleep.2019.02.007DOI Listing
February 2019
2 Reads

Computational Tools Unravel Putative Sterol Binding Sites in the Lysosomal NPC1 Protein.

J Chem Inf Model 2019 Apr 15. Epub 2019 Apr 15.

Department of Chemistry , Technische Universität Berlin , 10623 Berlin , Germany.

Two proteins have been linked as the critical components in the molecular mechanisms involved in the Niemann Pick type C (NPC) disease: NPC1, a 140 kDa polytopic membrane-bound protein, and the smaller (132 residues), water-soluble NPC2 protein. NPC1 is believed to act in tandem with NPC2, transferring cholesterol and other sterols out of the LE/Lys compartments. Mutations in either NPC1 or NPC2 can lead to an accumulation of cholesterol and lipids in the LE/Lys, the primary phenotype of the NPC disease, but approximately 95% of identified disease-causing mutations have been mapped to the membrane-bound NPC1 protein. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jcim.9b00186DOI Listing
April 2019
3 Reads

Hepatic and neuronal phenotype of NPC1 mice.

Heliyon 2019 Mar 14;5(3):e01293. Epub 2019 Mar 14.

QPS Austria GmbH, Parkring 12, 8074, Grambach, Austria.

Niemann-Pick type C disease (NPC) is a fatal autosomal recessive disorder characterized by a defect in the intracellular transport of lipoproteins leading to the accumulation of lipids in diverse tissues. A visceral and neuronal phenotype mimicking human NPC1 disease has been described in NPC1 mutant mice. These mice are by now the most widely used NPC1 rodent model to study NPC and developmental compounds against this devastating disease. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.heliyon.2019.e01293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423819PMC
March 2019
1 Read

Different Niemann-Pick C1 Genotypes Generate Protein Phenotypes that Vary in their Intracellular Processing, Trafficking and Localization.

Sci Rep 2019 Mar 28;9(1):5292. Epub 2019 Mar 28.

Department of Physiological Chemistry, University of Veterinary Medicine Hannover, 30559, Hannover, Germany.

Niemann-Pick Type C (NP-C) is an inherited neurovisceral lysosomal storage disease characterized by a defect in the trafficking of endocytosed cholesterol. In 95% of patients the gene encoding NPC1 is affected. The correlation of the genetic background in NP-C with the clinical phenotype such as, severity and onset of liver dysfunction, ataxia, dystonia and vertical gaze palsy, has not been elucidated at the molecular level. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-41707-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438969PMC
March 2019
2 Reads

The Effects of Liver Transplantation in Children with Niemann-Pick Disease Type B.

Liver Transpl 2019 Mar 26. Epub 2019 Mar 26.

Department of Liver Surgery, Ren Ji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.

We evaluated the effects of liver transplantation in children with Niemann-Pick disease (NPD) type B. From October 2006 to October 2018, 7 of 1512 children that received liver transplantation at Ren Ji Hospital were diagnosed as NPD type B. The median age at diagnosis is 12-month (6-14 months) with initial presentations of hepatosplenomegaly, growth retardation, repeated pneumonia and diarrhea. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/lt.25457DOI Listing
March 2019
2 Reads

Niemann-Pick type C1-related protein is a druggable target required for parasite membrane homeostasis.

Elife 2019 Mar 19;8. Epub 2019 Mar 19.

Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, Saint Louis, United States.

parasites possess a protein with homology to Niemann-Pick Type C1 proteins (Niemann-Pick Type C1-Related protein, NCR1). We isolated parasites with resistance-conferring mutations in NCR1 (PfNCR1) during selections with three diverse small-molecule antimalarial compounds and show that the mutations are causative for compound resistance. PfNCR1 protein knockdown results in severely attenuated growth and confers hypersensitivity to the compounds. Read More

View Article

Download full-text PDF

Source
https://elifesciences.org/articles/40529
Publisher Site
http://dx.doi.org/10.7554/eLife.40529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424564PMC
March 2019
5 Reads

Quantitative, Label-Free Proteomics in the Symptomatic Niemann-Pick, Type C1 Mouse Model Using Standard Flow Liquid Chromatography and Thermal Focusing Electrospray Ionization.

Proteomics 2019 Mar 19:e1800432. Epub 2019 Mar 19.

Department of Chemistry, University of Illinois at Chicago, Chicago, IL, 60607, USA.

Niemann-Pick disease, type C1 (NPC1) is a fatal, autosomal recessive, neurodegenerative disorder caused by mutations in the NPC1 gene. As a result, there is accumulation of unesterified cholesterol and sphingolipids in the late endosomal/lysosomal system. This abnormal accumulation results in a cascade of pathophysiological events including progressive, cerebellar neurodegeneration, among others. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/pmic.201800432DOI Listing
March 2019
2 Reads

Animal models for Niemann-Pick type C: implications for drug discovery & development.

Expert Opin Drug Discov 2019 May 19;14(5):499-509. Epub 2019 Mar 19.

a Orphazyme A/S , Copenhagen , Denmark.

Introduction: Niemann-Pick type C (NPC) is a neurovisceral, progressively detrimental lysosomal storage disease with very limited therapeutic options and no approved treatment available in the US. Despite its rarity, NPC has seen increased drug developmental efforts over the past decade, culminating in the completion of two potential registration trials in 2018. Areas covered: This review highlights the many available animal models that have been developed in the field and briefly covers classical and new cell technologies. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1080/17460441.2019.1588882DOI Listing
May 2019
1 Read

Diagnostic performance evaluation of sulfate-conjugated cholesterol metabolites as urinary biomarkers of Niemann-Pick disease type C.

Clin Chim Acta 2019 Mar 12;494:58-63. Epub 2019 Mar 12.

Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan; Faculty of Pharmaceutical Sciences, Tohoku University, 1-1 Seiryo-machi, Aoba-Ku, Sendai 980-8574, Japan.

Background: Niemann-Pick disease type C (NPC) is an autosomal recessive inherited disorder with progressive neuronal degeneration. Because conventional diagnostic methods are complicated and invasive, biomarker tests have drawn attention. We aimed to evaluate three urinary conjugated cholesterol metabolites as diagnostic biomarkers for NPC. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2019.03.1610DOI Listing
March 2019
2 Reads

Cytosolic glucosylceramide regulates endolysosomal function in Niemann-Pick type C disease.

Neurobiol Dis 2019 Mar 12;127:242-252. Epub 2019 Mar 12.

School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9BH, UK. Electronic address:

Niemann-Pick type C disease (NPCD) is a neurodegenerative disease associated with increases in cellular cholesterol and glycolipids and most commonly caused by defective NPC1, a late endosomal protein. Using ratiometric probes we find that NPCD cells show increased endolysosomal pH. In addition U18666A, an inhibitor of NPC1, was found to increase endolysosomal pH, and the number, size and heterogeneity of endolysosomal vesicles. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nbd.2019.03.005DOI Listing
March 2019
3 Reads
5.078 Impact Factor

Differential Proteomics Reveals miR-155 as a Novel Indicator of Liver and Spleen Pathology in the Symptomatic Niemann-Pick Disease, Type C1 Mouse Model.

Molecules 2019 Mar 12;24(5). Epub 2019 Mar 12.

Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA.

Niemann-Pick disease, type C1 (NPC1) is a rare, autosomal recessive, lipid storage disorder caused by mutations in . As a result, there is accumulation of unesterified cholesterol and sphingolipids in the late endosomal/lysosomal system. Clinically, patients can present with splenomegaly and hepatomegaly. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules24050994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429457PMC
March 2019
1 Read

Proteomics of the corpus callosum to identify novel factors involved in hypomyelinated Niemann-Pick Type C disease mice.

Mol Brain 2019 03 11;12(1):17. Epub 2019 Mar 11.

Albrecht-Kossel-Institute for Neuroregeneration, University Medical Center Rostock, Gehlsheimer Strasse 20, 18147, Rostock, Germany.

Hypomyelination in the central nerves system (CNS) is one of the most obviously pathological features in Niemann-Pick Type C disease (NPC), which is a rare neurodegenerative disorder caused by mutations in the NPC intracellular cholesterol transporter 1 or 2 (Npc1 or Npc2). Npc1 plays key roles in both neurons and oligodendrocytes during myelination, however, the linkage between the disturbed cholesterol transport and inhibited myelination is unrevealed. In this study, mass spectrometry (MS)-based differential quantitative proteomics was applied to compare protein composition in the corpus callosum between wild type (WT) and NPC mice. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13041-019-0440-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417209PMC

Cereal fiber improves blood cholesterol profiles and modulates intestinal cholesterol metabolism in C57BL/6 mice fed a high-fat, high-cholesterol diet.

Food Nutr Res 2019 25;63. Epub 2019 Feb 25.

Department of Nutrition and Food Hygiene, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Disease, School of Public Health, Soochow University, Suzhou, China.

Background: Dietary intake of cereal fiber has been reported to benefit lipid metabolism through multiple mechanisms. The present study aimed to discover the potential mechanisms by which cereal fiber could modify the intestinal cholesterol metabolism.

Design: Male C57BL/6 mice were fed a reference chow (RC) diet; high-fat, high-cholesterol (HFC) diet; HFC plus oat fiber diet; or HFC plus wheat bran fiber diet for 24 weeks. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.29219/fnr.v63.1591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403461PMC
February 2019
2 Reads

Evaluation of age of death in Niemann-Pick disease, type C: Utility of disease support group websites to understand natural history.

Mol Genet Metab 2019 Feb 15. Epub 2019 Feb 15.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, DHHS, Bethesda, MD, USA. Electronic address:

Niemann-Pick disease, type C (NPC) is a neurodegenerative lysosomal storage disease affecting the visceral organs and the central nervous system. The age of initial presentation varies from fetal to adult onset, although childhood onset is most common. The life expectancy for the full spectrum of NPC patients is not well defined, and it is unknown if current supportive care impacts the natural history. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ymgme.2019.02.004DOI Listing
February 2019
4 Reads

Imaging of changes in copper trafficking and redistribution in a mouse model of Niemann-Pick C disease using positron emission tomography.

Biometals 2019 04 7;32(2):293-306. Epub 2019 Mar 7.

School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas' Hospital, London, SE1 7EH, UK.

Niemann-Pick C disease (NPC) is an autosomal recessive lysosomal storage disorder resulting from mutations in the NPC1 (95% of cases) or NPC2 genes. Disturbance of copper homeostasis has been reported in NPC1 disease. In this study we have used whole-body positron emission tomography (PET) and brain electronic autoradiography with copper-64 (Cu), in the form of the copper(II) bis(thiosemicarbazonato) complex Cu-GTSM, to image short-term changes in copper trafficking after intravenous injection in a transgenic mouse model of NPC1 disease. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10534-019-00185-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437134PMC
April 2019
1 Read
2.503 Impact Factor

In Vitro and In Vivo Evaluation of 6-O-α-Maltosyl-β-Cyclodextrin as a Potential Therapeutic Agent Against Niemann-Pick Disease Type C.

Int J Mol Sci 2019 Mar 6;20(5). Epub 2019 Mar 6.

Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.

Niemann-Pick disease Type C (NPC) is a rare lysosomal storage disease characterized by the dysfunction of intracellular cholesterol trafficking with progressive neurodegeneration and hepatomegaly. We evaluated the potential of 6--α-maltosyl-β-cyclodextrin (G2-β-CD) as a drug candidate against NPC. The physicochemical properties of G2-β-CD as an injectable agent were assessed, and molecular interactions between G2-β-CD and free cholesterol were studied by solubility analysis and two-dimensional proton nuclear magnetic resonance spectroscopy. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20051152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429330PMC
March 2019
2 Reads

Niemann-Pick Disease Type C: Mutation Spectrum and Novel Sequence Variations in the Human NPC1 Gene.

Mol Neurobiol 2019 Feb 28. Epub 2019 Feb 28.

Laboratório de Identificação Genética, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.

Niemann-Pick type C (NP-C) is a rare autosomal recessive disorder characterized by storage of unesterified glycolipids and cholesterol in lysosome and/or late endosome due to mutations in either NPC1 or NPC2 gene. This study aims to identify the spectrum of sequence alterations associated to NP-C in individuals with clinical suspicion of this disease. The entire coding region and flanking sequences of both genes associated to NP-C were evaluated in a total of 265 individuals that were referred to our laboratory. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-019-1528-zDOI Listing
February 2019
1 Read

Liposome-targeted recombinant human acid sphingomyelinase: Production, formulation, and in vitro evaluation.

Eur J Pharm Biopharm 2019 Apr 25;137:185-195. Epub 2019 Feb 25.

Department of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, the Netherlands. Electronic address:

Niemann-Pick disease type B is a hereditary rare condition caused by deficiency of the acid sphingomyelinase (ASM) that is needed for lysosomal hydrolysis of sphingomyelin to ceramide and phosphocholine. This deficiency leads to a massive accumulation of sphingomyelin in cells throughout the body, predominantly in the liver, spleen and lungs. Currently, there is no effective treatment available. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpb.2019.02.019DOI Listing

Co-treatment with probucol does not improve lung pathology in hydroxypropyl-β-cyclodextrin-treated Npc1 mice.

J Appl Genet 2019 Feb 28. Epub 2019 Feb 28.

Department of pediatrics, University of Arizona College of medicine, Tucson, AZ, 85724, USA.

We previously reported the altered pulmonary function and pathology found in the mouse model of infantile Niemann-Pick C1 disease, the Npc1 mouse. Despite its salutary properties on brain and liver parameters, we did not find efficacious effects of hydroxypropyl-β-cyclodextrin (HPBCD) on pulmonary pathology. Since we had previously shown the beneficial effects of probucol on the somatic phenotype in the Npc1 mice, we have now studied the effects of combined therapy with HPBCD and probucol on the lung with mostly negative results. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13353-019-00487-xDOI Listing
February 2019
1 Read

Chronic visceral acid sphingomyelinase deficiency (Niemann-Pick disease type B) in 16 Polish patients: long-term follow-up.

Orphanet J Rare Dis 2019 02 22;14(1):55. Epub 2019 Feb 22.

Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.

Background: Acid sphingomyelinase deficiency (ASMD), due to mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene, is divided into infantile neurovisceral ASMD (Niemann-Pick type A), chronic neurovisceral ASMD (intermediate form, Niemann-Pick type A/B) and chronic visceral ASMD (Niemann-Pick type B). We conducted a long-term observational, single-center study including 16 patients with chronic visceral ASMD.

Results: 12 patients were diagnosed in childhood and 4 others in adulthood, the oldest at the age of 50. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13023-019-1029-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387484PMC
February 2019
3 Reads

Purification and Characterization of Human Niemann-Pick C1 Protein.

Methods Mol Biol 2019 ;1949:257-267

Department of Molecular Biology, Princeton University, Princeton, NJ, USA.

Niemann-Pick C1 (NPC1) is a membrane protein required for the transport of low-density lipoprotein (LDL)-derived cholesterol from endosomes and lysosomes to the other organelles. Here, we describe the recombinant protein expression, purification, and characterization of the human NPC1. The protein is transiently expressed in human embryonic kidney (HEK) cells. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-4939-9136-5_18DOI Listing
January 2019

Mechanisms of Niemann-Pick type C1 Like 1 protein degradation in intestinal epithelial cells.

Am J Physiol Cell Physiol 2019 Apr 21;316(4):C559-C566. Epub 2019 Feb 21.

Jesse Brown Veterans Affairs Medical Center , Chicago, Illinois.

Intestinal Niemann-Pick C1 Like 1 (NPC1L1) protein plays a key role in cholesterol absorption. A decrease in NPC1L1 expression has been implicated in lowering plasma cholesterol and mitigating the risk for coronary heart disease. Little is known about the mechanisms responsible for NPC1L1 protein degradation that upon activation may lead to a reduction in NPC1L1 protein levels in intestinal epithelial cells (IECs). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpcell.00465.2018DOI Listing
April 2019
8 Reads

Mitochondrial biogenesis is transcriptionally repressed in lysosomal lipid storage diseases.

Elife 2019 Feb 18;8. Epub 2019 Feb 18.

Institute of Cellular Biochemistry, University Medical Center Goettingen, Goettingen, Germany.

Perturbations in mitochondrial function and homeostasis are pervasive in lysosomal storage diseases, but the underlying mechanisms remain unknown. Here, we report a transcriptional program that represses mitochondrial biogenesis and function in lysosomal storage diseases Niemann-Pick type C (NPC) and acid sphingomyelinase deficiency (ASM), in patient cells and mouse tissues. This mechanism is mediated by the transcription factors KLF2 and ETV1, which are both induced in NPC and ASM patient cells. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.39598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379092PMC
February 2019
2 Reads

Lysosomal storage disease overview.

Authors:
Angela Sun

Ann Transl Med 2018 Dec;6(24):476

Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.

The lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders that are caused for the most part by enzyme deficiencies within the lysosome resulting in accumulation of undegraded substrate. This storage process leads to a broad spectrum of clinical manifestations depending on the specific substrate and site of accumulation. Examples of LSDs include the mucopolysaccharidoses, mucolipidoses, oligosaccharidoses, Pompe disease, Gaucher disease, Fabry disease, the Niemann-Pick disorders, and neuronal ceroid lipofuscinoses. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm.2018.11.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331358PMC
December 2018
5 Reads

A case of Niemann-Pick disease type C with neonatal liver failure initially diagnosed as neonatal hemochromatosis.

Brain Dev 2019 May 6;41(5):460-464. Epub 2019 Feb 6.

Division of Neurology, National Center for Child Health and Development, Tokyo, Japan.

Background: Niemann-Pick type C (NPC) is a lysosomal lipid storage disease with mutation of NPC1/NPC2 genes, which transport lipids in the endosome and lysosome, and various neurological symptoms. NPC patients also develop hepatosplenomegaly or liver disorder in the neonatal period, and 10% suffer severe liver failure. Neonatal hemochromatosis (NH) is a liver disorder characterized by hepatic and extrahepatic siderosis. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.braindev.2019.01.004DOI Listing
May 2019
2 Reads

Lipid⁻Protein Interactions in Niemann⁻Pick Type C Disease: Insights from Molecular Modeling.

Int J Mol Sci 2019 Feb 7;20(3). Epub 2019 Feb 7.

School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9BH, UK.

The accumulation of lipids in the late endosomes and lysosomes of Niemann⁻Pick type C disease (NPCD) cells is a consequence of the dysfunction of one protein (usually NPC1) but induces dysfunction in many proteins. We used molecular docking to propose (a) that NPC1 exports not just cholesterol, but also sphingosine, (b) that the cholesterol sensitivity of big potassium channel (BK) can be traced to a previously unappreciated site on the channel's voltage sensor, (c) that transient receptor potential mucolipin 1 (TRPML1) inhibition by sphingomyelin is likely an indirect effect, and (d) that phosphoinositides are responsible for both the mislocalization of annexin A2 (AnxA2) and a soluble NSF (N-ethylmaleimide Sensitive Fusion) protein attachment receptor (SNARE) recycling defect. These results are set in the context of existing knowledge of NPCD to sketch an account of the endolysosomal pathology key to this disease. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20030717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387118PMC
February 2019
3 Reads

Disease characteristics, prognosis and miglustat treatment effects on disease progression in patients with Niemann-Pick disease Type C: an international, multicenter, retrospective chart review.

Orphanet J Rare Dis 2019 01;14(1):32

Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.

Background: Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder characterized by progressive neurodegenerative symptomatology. The signs and symptoms of NP-C vary with age at disease onset, and available therapies are directed at alleviating symptoms and stabilizing disease progression. We report the characteristics and factors related to disease progression, and analyze the effect of miglustat treatment on disease progression and patient survival using NP-C disability scales. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13023-019-0996-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367842PMC
January 2019
4 Reads
3.358 Impact Factor

The atypical antipsychotic quetiapine induces hyperlipidemia by activating intestinal PXR signaling.

JCI Insight 2019 Feb 7;4(3). Epub 2019 Feb 7.

Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky, USA.

Quetiapine, one of the most prescribed atypical antipsychotics, has been associated with hyperlipidemia and an increased risk for cardiovascular disease in patients, but the underlying mechanisms remain unknown. Here, we identified quetiapine as a potent and selective agonist for pregnane X receptor (PXR), a key nuclear receptor that regulates xenobiotic metabolism in the liver and intestine. Recent studies have indicated that PXR also plays an important role in lipid homeostasis. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.125657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413802PMC
February 2019
4 Reads

ROS Scavenger, Ebselen, Has No Preventive Effect in New Hearing Loss Model Using a Cholesterol-Chelating Agent.

J Audiol Otol 2019 Apr 8;23(2):69-75. Epub 2019 Feb 8.

Department of Otorhinolaryngology, Boramae Medical Center, Seoul Metropolitan Government-Seoul National University, Seoul, Korea.

Background And Objectives: The antioxidant ebselen will be able to limit or prevent the ototoxicity arising from 2-hydroxypropyl-β-cyclodextrin (HPβCD). Niemann-Pick Type C (NPC) disease is a disorder of lysosomal storage manifested in sphingolipidosis. Recently, it was noted that experimental use of HPβCD could partially resolve the symptoms in both animals and human patients. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.7874/jao.2018.00255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468279PMC
April 2019
3 Reads

[Intracellularly Degradable Polyrotaxanes for Therapeutic Applications].

Authors:
Atsushi Tamura

Yakugaku Zasshi 2019 ;139(2):143-155

Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU).

Recently, the application of β-cyclodextrins (β-CDs) as therapeutic agents has received considerable attention. β-CDs have been reported to have therapeutic effects on various diseases, such as Niemann-Pick type C (NPC) disease, a family of lysosomal storage disorders characterized by the lysosomal accumulation of cholesterol. To further improve the therapeutic efficacy of β-CDs, the use of β-CD-threaded polyrotaxanes (PRXs) has been proposed as a carrier of β-CDs for NPC disease. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1248/yakushi.18-00168-1DOI Listing
January 2019
2 Reads

NPC intracellular cholesterol transporter 1 (NPC1)-mediated cholesterol export from lysosomes.

J Biol Chem 2019 02;294(5):1706-1709

From the Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305-5307

Low-density lipoprotein particles are taken up by cells and delivered to the lysosome where their cholesterol esters are cleaved off by acid lipase. The released, free cholesterol is then exported from lysosomes for cellular needs or storage. This article summarizes recent advances in our understanding of the molecular basis of cholesterol export from lysosomes. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.TM118.004165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364775PMC
February 2019
2 Reads

Cyclodextrin triggers MCOLN1-dependent endo-lysosome secretion in Niemann-Pick type C cells.

J Lipid Res 2019 Apr 1;60(4):832-843. Epub 2019 Feb 1.

Department of Biochemistry, University of Geneva, 1211-Geneva-4, Switzerland

In specialized cell types, lysosome-related organelles support regulated secretory pathways, whereas in nonspecialized cells, lysosomes can undergo fusion with the plasma membrane in response to a transient rise in cytosolic calcium. Recent evidence also indicates that lysosome secretion can be controlled transcriptionally and promote clearance in lysosome storage diseases. In addition, evidence is also accumulating that low concentrations of cyclodextrins reduce the cholesterol-storage phenotype in cells and animals with the cholesterol storage disease Niemann-Pick type C, via an unknown mechanism. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1194/jlr.M089979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446697PMC
April 2019
2 Reads

Metabolic liver diseases presenting with neonatal cholestasis: at the crossroad between old and new paradigms.

Eur J Pediatr 2019 Apr 28;178(4):515-523. Epub 2019 Jan 28.

Pediatric Gastroenterology Unit, Centro Materno Infantil do Norte - CMIN, Centro Hospitalar Universitário do Porto, Largo da Maternidade de Júlio Dinis, 4050-651, Porto, Portugal.

Metabolic liver diseases (MLD) are an important group of disorders presenting with neonatal cholestasis (NC). The spectrum of liver involvement is wide and the presumptive diagnosis is traditionally based on clinical and laboratory findings. Recently, next-generation sequencing (NGS) panels have emerged as an appealing tool to diagnose neonatal/infantile cholestatic disorders. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00431-019-03328-5DOI Listing
April 2019
2 Reads

Imaging of tau deposits in adults with Niemann-Pick type C disease: a case-control study.

Eur J Nucl Med Mol Imaging 2019 May 28;46(5):1132-1138. Epub 2019 Jan 28.

The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia.

Purpose: Niemann-Pick type C (NPC) is a cholesterol storage disease characterized by disruption in the endosomal-lysosomal transport system that leads to the accumulation of cholesterol and glycolipids in lysosomes. Developmental cognitive delay and progressive motor and cognitive impairment are characteristic of the disease. Tau accumulation has been reported in some NPC patients. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-019-4273-7DOI Listing
May 2019
3 Reads

Inhibition of Niemann-Pick C1-Like 1 by Ezetimibe Reduces Dietary 5β,6β-Epoxycholesterol Absorption in Rats.

Cardiovasc Drugs Ther 2019 Feb;33(1):35-44

Laboratory of Nutrition Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.

Purpose: Oxycholesterols (OCs) are produced from cholesterol by oxidation of the steroidal backbone and side-chain. OCs are present in blood and evidence suggests their involvement in disease development and progression. However, limited information is available regarding the absorption mechanisms and relative absorption rates of dietary OCs. Read More

View Article

Download full-text PDF

Source
http://link.springer.com/10.1007/s10557-019-06854-4
Publisher Site
http://dx.doi.org/10.1007/s10557-019-06854-4DOI Listing
February 2019
9 Reads

Niemann-Pick proteins type C2 are identified as olfactory related genes of Pardosa pseudoannulata by transcriptome and expression profile analysis.

Comp Biochem Physiol Part D Genomics Proteomics 2019 Mar 17;29:320-329. Epub 2019 Jan 17.

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China. Electronic address:

In arthropods, the large majority of studies on olfaction have been mainly focused on insects, whereas little on Arachnida, even though olfaction is very important in arachnid behavior. Pardosa pseudoannulata is one of the most common wandering spiders in rice fields, as the important natural enemy against a range of pests. However, little is known about the potential chemosensory proteins involved in olfactory behavior of these spiders. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cbd.2019.01.004DOI Listing
March 2019
1 Read

Pneumococcal Immunization Reduces Neurological and Hepatic Symptoms in a Mouse Model for Niemann-Pick Type C1 Disease.

Front Immunol 2018 7;9:3089. Epub 2019 Jan 7.

Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands.

Niemann-Pick type C1 (NPC1) disease is caused by a deleterious mutation in the gene, causing lysosomal accumulation of unesterified cholesterol and sphingolipids. Consequently, NPC1 disease patients suffer from severe neurovisceral symptoms which, in the absence of effective treatments, result in premature death. NPC1 disease patients display increased plasma levels of cholesterol oxidation products such as those enriched in oxidized low-density lipoprotein (oxLDL), a pro-inflammatory mediator. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2018.03089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330339PMC
January 2019
3 Reads

Recommendations for patient screening in ultra-rare inherited metabolic diseases: what have we learned from Niemann-Pick disease type C?

Orphanet J Rare Dis 2019 01 21;14(1):20. Epub 2019 Jan 21.

University of Pretoria, Pretoria, South Africa.

Background: Rare and ultra-rare diseases (URDs) are often chronic and life-threatening conditions that have a profound impact on sufferers and their families, but many are notoriously difficult to detect. Niemann-Pick disease type C (NP-C) serves to illustrate the challenges, benefits and pitfalls associated with screening for ultra-rare inborn errors of metabolism (IEMs). A comprehensive, non-systematic review of published information from NP-C screening studies was conducted, focusing on diagnostic methods and study designs that have been employed to date. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13023-018-0985-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341610PMC
January 2019
6 Reads

Canis familiaris allergen Can f 7: Expression, purification and analysis of B cell epitopes in Chinese children with dog allergies.

Int J Mol Med 2019 Mar 15;43(3):1531-1541. Epub 2019 Jan 15.

Research Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.

Dogs are a major source of indoor allergens. However, the prevalence of dog allergies in China remains unclear, especially in children. In the present study, Can f 7, a canine allergen belonging to the Niemann pick type C2 protein family, was selected to study its sensitization rate in Chinese children with dog allergies. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijmm.2019.4065DOI Listing
March 2019
2 Reads
1.880 Impact Factor

Molecular Pathways and Respiratory Involvement in Lysosomal Storage Diseases.

Int J Mol Sci 2019 Jan 15;20(2). Epub 2019 Jan 15.

Rare Metabolic Diseases Unit, Pediatric Department, Fondazione MBBM, Università degli Studi di Milano Bicocca, San Gerardo Hospital, ASST di Monza, 20900 Monza, Italy.

Lysosomal storage diseases (LSD) include a wide range of different disorders with variable degrees of respiratory system involvement. The purpose of this narrative review is to treat the different types of respiratory manifestations in LSD, with particular attention being paid to the main molecular pathways known so far to be involved in the pathogenesis of the disease. A literature search was conducted using the Medline/PubMed and EMBASE databases to identify studies, from 1968 through to November 2018, that investigated the respiratory manifestations and molecular pathways affected in LSD. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20020327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359090PMC
January 2019
2 Reads

Diverse Chemical Compounds Target Plasmodium falciparum Plasma Membrane Lipid Homeostasis.

ACS Infect Dis 2019 Apr 28;5(4):550-558. Epub 2019 Jan 28.

Center for Molecular Parasitology, Department of Microbiology and Immunology , Drexel University College of Medicine , 2900 Queen Lane , Philadelphia , Pennsylvania 19129 , United States of America.

Lipid homeostasis is essential to the maintenance of life. We previously reported that disruptions of the parasite Na homeostasis via inhibition of PfATP4 resulted in elevated cholesterol within the parasite plasma membrane as assessed by saponin sensitivity. A large number of compounds have been shown to target the parasite Na homeostasis. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsinfecdis.8b00277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461493PMC
April 2019
1 Read

Is autophagy an elective strategy to protect neurons from dysregulated cholesterol metabolism?

Neural Regen Res 2019 Apr;14(4):582-587

Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.

The balance of autophagy, apoptosis and necroptosis is crucial to determine the outcome of the cellular response to cholesterol dysregulation. Cholesterol plays a major role in regulating the properties of cell membranes, especially as regards their fluidity, and the regulation of its biosynthesis influences the shape and functions of these membranes. Whilst dietary cholesterol can easily be distributed to most organs, the central nervous system, whose membranes are particularly rich in cholesterol, mainly relies on de novo synthesis. Read More

View Article

Download full-text PDF

Source
http://www.nrronline.org/text.asp?2019/14/4/582/247441
Publisher Site
http://dx.doi.org/10.4103/1673-5374.247441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352582PMC
April 2019
37 Reads

Psychiatric and Cognitive Symptoms Associated with Niemann-Pick Type C Disease: Neurobiology and Management.

CNS Drugs 2019 Feb;33(2):125-142

Neuropsychiatry Unit, The Royal Melbourne Hospital, Melbourne, VIC, Australia.

Niemann-Pick disease type C (NPC) is a lysosomal storage disorder that presents with a spectrum of clinical manifestations from infancy and childhood or in early or mid-adulthood. Progressive neurological symptoms including ataxia, dystonia and vertical gaze palsy are a hallmark of the disease, and psychiatric symptoms such as psychosis and mood disorders are common. These latter symptoms often present early in the course of NPC and thus these patients are often diagnosed with a major psychotic or affective disorder before neurological and cognitive signs present and the diagnosis is revised. Read More

View Article

Download full-text PDF

Source
http://link.springer.com/10.1007/s40263-018-0599-0
Publisher Site
http://dx.doi.org/10.1007/s40263-018-0599-0DOI Listing
February 2019
19 Reads