3,227 results match your criteria Niemann-Pick Disease


First Prenatal Diagnosis of a Niemann-Pick Disease Type C2 Revealed by a Cystic Hygroma: A Case Report and Review of the Literature.

Front Endocrinol (Lausanne) 2018 6;9:292. Epub 2018 Jun 6.

Faculty of Medicine, Transilvania University of Brasov, Brasov, Romania.

Background: The importance of fetal nuchal translucency was highlighted in the early 1990s as a useful first-trimester marker to identify fetal chromosomal abnormalities. Here, we report the prenatal diagnosis of a fetus with Niemann-Pick disease type C initially identified by first-trimester ultrasonographic markers and eventually confirmed by extensive genetic evaluation.

Case Presentation: The fetus of a 30-year-old woman exhibited a cystic hygroma in the first trimester of pregnancy. Read More

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DPubChem: a web tool for QSAR modeling and high-throughput virtual screening.

Sci Rep 2018 Jun 14;8(1):9110. Epub 2018 Jun 14.

Computational Bioscience Research Center, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia.

High-throughput screening (HTS) performs the experimental testing of a large number of chemical compounds aiming to identify those active in the considered assay. Alternatively, faster and cheaper methods of large-scale virtual screening are performed computationally through quantitative structure-activity relationship (QSAR) models. However, the vast amount of available HTS heterogeneous data and the imbalanced ratio of active to inactive compounds in an assay make this a challenging problem. Read More

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The neuropathology of the adult cerebellum.

Authors:
Arnulf H Koeppen

Handb Clin Neurol 2018 ;154:129-149

Research, Neurology, and Pathology Services, Veterans Affairs Medical Center and Departments of Neurology and Pathology, Albany Medical College, Albany, NY, United States. Electronic address:

This chapter summarizes the neuropathologic features of nonneoplastic disorders of the adult cerebellum. Gait ataxia and extremity dysmetria are clinical manifestations of diseases that interrupt the complex cerebellar circuitry between the neurons of the cerebellar cortex, the cerebellar nuclei (especially the dentate nuclei), and the inferior olivary nuclei. The cerebellum is a prominent target of several sporadic and hereditary neurodegenerative diseases, including multiple system atrophy, spinocerebellar ataxia, and Friedreich ataxia. Read More

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January 2018
2 Reads

Absence of infiltrating peripheral myeloid cells in the brains of mouse models of lysosomal storage disorders.

J Neurochem 2018 Jun 14. Epub 2018 Jun 14.

Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 76100, Israel.

Approximately 70 lysosomal storage diseases are currently known, resulting from mutations in genes encoding lysosomal enzymes and membrane proteins. Defects in lysosomal enzymes that hydrolyze sphingolipids have been relatively well studied. Gaucher disease is caused by the loss of activity of glucocerebrosidase, leading to accumulation of glucosylceramide. Read More

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Transcriptional control of intestinal cholesterol absorption, adipose energy expenditure and lipid handling by Sortilin.

Sci Rep 2018 Jun 13;8(1):9006. Epub 2018 Jun 13.

Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.

The sorting receptor Sortilin functions in the regulation of glucose and lipid metabolism. Dysfunctional lipid uptake, storage, and metabolism contribute to several major human diseases including atherosclerosis and obesity. Sortilin associates with cardiovascular disease; however, the role of Sortilin in adipose tissue and lipid metabolism remains unclear. Read More

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Large pericardial effusion and tamponade in young male with Niemann-Pick disease type C.

Intern Med J 2018 Jun;48(6):742-744

Royal Melbourne Hospital, Melbourne, Victoria, Australia.

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Model construction of Niemann-Pick type C disease in zebrafish.

Biol Chem 2018 Jun 20. Epub 2018 Jun 20.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Donghu South Road 7#, Wuhan 430072, China.

Niemann-Pick type C disease (NPC) is a rare human disease, with limited effective treatment options. Most cases of NPC disease are associated with inactivating mutations of the NPC1 gene. However, cellular and molecular mechanisms responsible for the NPC1 pathogenesis remain poorly defined. Read More

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A 4-Week-old Neonate with Jaundice and Hepatosplenomegaly.

J Clin Exp Hepatol 2018 Jun 16;8(2):210-211. Epub 2017 Nov 16.

Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH 43205, USA.

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Metabolic ataxias.

Handb Clin Neurol 2018 ;155:117-127

Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD, United States. Electronic address:

The nervous system is vulnerable to intrinsic and extrinsic metabolic perturbations. In particular, the cerebellum, with its large Purkinje cells and its high density of neurons and glial cells, has high metabolic demand and is highly vulnerable to metabolic derangements. As a result, many disorders of intermediary metabolism will preferentially and sometimes selectively target the cerebellum. Read More

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January 2018

Niemann-Pick C1-deficient mice lacking sterol O-acyltransferase 2 have less hepatic cholesterol entrapment and improved liver function.

Am J Physiol Gastrointest Liver Physiol 2018 Jun 7. Epub 2018 Jun 7.

Department of Internal Medicine, University of Texas Southwestern Medical Center, United States.

Cholesteryl esters are generated at multiple sites in the body by sterol O-acyltransferase 1 (SOAT1) or sterol O-acyltransferase 2 (SOAT2) in various cell types, and lecithin cholesterol acyltransferase (LCAT) in plasma. Esterified cholesterol (EC) and triacylglycerol (TAG) contained in lipoproteins cleared from the circulation via receptor-mediated or bulk-phase endocytosis are hydrolyzed by lysosomal acid lipase (LAL) within the late endosomal/lysosomal (E/L) compartment. Then, through the successive actions of Niemann-Pick C2 (NPC2) and Niemann-Pick C1 (NPC1), unesterified cholesterol (UC) is exported from the E/L compartment to the cytosol. Read More

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June 2018
4 Reads

AAV9 intracerebroventricular gene therapy improves lifespan, locomotor function and pathology in a mouse model of Niemann-Pick type C1 disease.

Hum Mol Genet 2018 Jun 5. Epub 2018 Jun 5.

Department of Pharmacology, UCL School of Pharmacy, University College London, London, WC1N 1AX, UK.

Niemann-Pick type C disease (NP-C) is a fatal neurodegenerative lysosomal storage disorder. It is caused in 95% of cases by a mutation in the NPC1 gene that encodes NPC1, an integral transmembrane protein localised to the limiting membrane of the lysosome. There is no cure for NP-C but there is a disease-modifying drug (miglustat) that slows disease progression but with associated side effects. Read More

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June 2018
1 Read

Distinguishing neurocognitive deficits in adult patients with NP-C from early onset Alzheimer's dementia.

Orphanet J Rare Dis 2018 Jun 5;13(1):91. Epub 2018 Jun 5.

Department of Neurology, University Hospital of Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany.

Background: Niemann-Pick disease type C (NP-C) is a rare, progressive neurodegenerative disease caused by mutations in the NPC1 or the NPC2 gene. Neurocognitive deficits are common in NP-C, particularly in patients with the adolescent/adult-onset form. As a disease-specific therapy is available, it is important to distinguish clinically between the cognitive profiles in NP-C and primary dementia (e. Read More

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June 2018
2 Reads

Cholesterol impairs autophagy-mediated clearance of amyloid beta while promoting its secretion.

Autophagy 2018 Jun 4:1-26. Epub 2018 Jun 4.

a Department of Cell Death and Proliferation , Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) , Barcelona , Spain.

Macroautophagy/autophagy failure with the accumulation of autophagosomes is an early neuropathological feature of Alzheimer disease (AD) that directly affects amyloid beta (Aβ) metabolism. Although loss of presenilin 1 function has been reported to impair lysosomal function and prevent autophagy flux, the detailed mechanism leading to autophagy dysfunction in AD remains to be elucidated. The resemblance between pathological hallmarks of AD and Niemann-Pick Type C disease, including endosome-lysosome abnormalities and impaired autophagy, suggests cholesterol accumulation as a common link. Read More

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June 2018
2 Reads

Ezetimibe, a NPC1L1 inhibitor, attenuates neuronal apoptosis through AMPK dependent autophagy activation after MCAO in rats.

Exp Neurol 2018 May 28;307:12-23. Epub 2018 May 28.

Department of Anesthesiology and Basic Sciences, Loma Linda University, School of Medicine, Loma Linda, CA, USA. Electronic address:

Autophagy activation exerts neuroprotective effects in the ischemic stroke model. Ezetimibe (Eze), a Niemann-Pick disease type C1-Like 1 (NPC1L1) pharmacological inhibitor, has been reported to protect hepatocytes from apoptosis via autophagy activation. In this study, we explored whether Eze could attenuate neuronal apoptosis in the rat model of middle cerebral artery occlusion (MCAO), specifically via activation of the AMPK/ULK1/autophagy pathway. Read More

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May 2018
3 Reads

Macula halo syndrome.

Int Ophthalmol 2018 May 29. Epub 2018 May 29.

Bakirkoy Dr. Sadi Konuk Training & Research Hospital, İstanbul, Turkey.

Introduction: Niemann-Pick disease (NPD) is a hereditary lysosomal storage disorder in which mutations in the sphingomyelin phosphodiesterase gene leads to partial or complete deficiency of the sphingomyelinase enzyme. Niemann-Pick Type B is the intermediate form associated with hepatosplenomegaly, foam cells in the bone marrow, hyperlipidemia and diffuse pulmonary infiltrates, which is generally diagnosed in late adolescence. Central nervous system is not affected, and some cases may display macular halo. Read More

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May 2018
1 Read

Cyclodextrins: Assessing the Impact of Cavity Size, Occupancy, and Substitutions on Cytotoxicity and Cholesterol Homeostasis.

Molecules 2018 May 20;23(5). Epub 2018 May 20.

Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN 37208, USA.

Cyclodextrins (CDs) are cyclic oligosaccharides; the most common CDs contain six, seven, or eight glucose units called α-CDs, β-CDs, and γ-CDs, respectively. The use of CDs in biomedical research is increasing due to their ability to interact with membrane lipids as well as a wide variety of poorly water-soluble molecules. We assessed the impact of CD cavity size, occupancy, and substitutions on cytotoxicity and cholesterol homeostasis. Read More

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May 2018
3 Reads

Genetic polymorphism of sterol transporters in children with future gallstones.

Dig Liver Dis 2018 Apr 26. Epub 2018 Apr 26.

Pediatric Surgery, Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

Background & Aims: Gallstone disease is related to hypersecretion of cholesterol in bile, and low serum phytosterol levels. We examined how genetic polymorphisms of sterol transporters affect childhood cholesterol metabolism trait predicting adult gallstone disease.

Patients And Methods: In retrospective controlled study, we determined D19H polymorphism of ABCG8 gene, genetic variation at Niemann-Pick C1-like 1 (NPC1L1) gene locus (rs41279633, rs17655652, rs2072183, rs217434 and rs2073548), and serum cholesterol, noncholesterol sterols and lipids in children affected by gallstones decades later (n = 66) and controls (n = 126). Read More

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April 2018
1 Read

CCDC115-CDG: A new rare and misleading inherited cause of liver disease.

Mol Genet Metab 2018 May 9. Epub 2018 May 9.

AP-HP, Bichat University Hospital, Biochemistry, Paris, France; INSERM UMR-1193 "Mécanismes cellulaires et moléculaires de l'adaptation au stress et cancérogenèse", Université Paris-Sud, Châtenay-Malabry, France. Electronic address:

Congenital disorders of glycosylation (CDG) linked to defects in Golgi apparatus homeostasis constitute an increasing part of these rare inherited diseases. Among them, COG-CDG, ATP6V0A2-CDG, TMEM199-CDG and CCDC115-CDG have been shown to disturb Golgi vesicular trafficking and/or lumen pH acidification. Here, we report 3 new unrelated cases of CCDC115-CDG with emphasis on diagnosis difficulties related to strong phenotypic similarities with mitochondriopathies, Niemann-Pick disease C and Wilson Disease. Read More

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May 2018
12 Reads

Improvement of impaired electrical activity in NPC1 mutant cortical neurons upon DHPG stimulation detected by micro-electrode array.

Brain Res 2018 May 10. Epub 2018 May 10.

Albrecht-Kossel-Institute for Neuroregeneration, Rostock University Medical Center, Gehlsheimer Straße 20, 18147 Rostock, Germany; Centre for Transdisciplinary Neuroscience Rostock, Rostock University Medical Center, Gehlsheimer Straße 20, 18147 Rostock, Germany. Electronic address:

Niemann-Pick Type C1 (NPC1) disease is an autosomal recessive neurodegenerative disease characterized by an excessive accumulation of unesterified cholesterol in late endosomes/lysosomes. Patients with NPC1 disease show a series of symptoms in neuropathology, including a gradually increased loss of motor control and seizures. However, mechanism of the neurological manifestations in NPC1 disease is not fully understood yet. Read More

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May 2018
2 Reads

Ganglioside Metabolism in Health and Disease.

Prog Mol Biol Transl Sci 2018 28;156:1-62. Epub 2018 Mar 28.

Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany. Electronic address:

Gangliosides (GGs) are cell type-specific sialic acid-containing glycosphingolipids (GSLs), which are enriched in mammalian brain. Defects in GSL metabolism cause fatal human diseases. GSLs are composed of a hydrophilic oligosaccharide linked in 1-O-position to a hydrophobic ceramide anchor, which itself is composed of a long-chain amino alcohol, the sphingoid base, and an amide-bound acyl chain. Read More

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March 2018
1 Read

Early Endosome Morphology in Health and Disease.

Adv Exp Med Biol 2018 ;1074:335-343

Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.

Early endosomes are organelles that receive macromolecules and solutes from the extracellular environment. The major function of early endosomes is to sort these cargos into recycling and degradative compartments of the cell. Degradation of the cargo involves maturation of early endosomes into late endosomes, which, after acquisition of hydrolytic enzymes, form lysosomes. Read More

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January 2018
2 Reads

The pathogenesis of lysosomal storage disorders: beyond the engorgement of lysosomes to abnormal development and neuroinflammation.

Hum Mol Genet 2018 Apr 28. Epub 2018 Apr 28.

Department of Pediatrics, University of Arizona, 1501 N Campbell Ave, Tucson, AZ, 85724-5073, USA.

There is growing evidence that the complex clinical manifestations of lysosomal storage diseases (LSDs) are not fully explained by the engorgement of the endosomal-autophagic-lysosomal system. In this review, we explore current knowledge of common pathogenetic mechanisms responsible for the early onset of tissue abnormalities of two LSDs, Mucopolysaccharidosis type II (MPSII) and Niemann-Pick type C (NPC) diseases. In particular, perturbations of the homeostasis of glycosaminoglycans (GAGs) and cholesterol (Chol) in MPSII and NPC diseases, respectively, affect key biological processes, including morphogen signaling. Read More

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The intersection of lysosomal and endoplasmic reticulum calcium with autophagy defects in lysosomal diseases.

Neurosci Lett 2018 Apr 25. Epub 2018 Apr 25.

Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, United States. Electronic address:

The lysosomal storage disorders (LSDs) encompass a group of more than 50 inherited diseases characterized by the accumulation of lysosomal substrates. Two-thirds of patients experience significant neurological symptoms, but the mechanisms of neurodegeneration are not well understood. Interestingly, a wide range of LSDs show defects in both autophagy and Ca homeostasis, which is notable as Ca is a key regulator of autophagy. Read More

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April 2018
1 Read

Endocannabinoids in Caenorhabditis elegans are essential for the mobilization of cholesterol from internal reserves.

Sci Rep 2018 Apr 23;8(1):6398. Epub 2018 Apr 23.

Laboratorio de Fisiología Microbiana, Instituto de Biología Molecular y Celular de Rosario (IBR), CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, 2000, Rosario, Argentina.

Proper cholesterol transport is crucial for the functionality of cells. In C. elegans, certain cholesterol derivatives called dafachronic acids (DAs) govern the entry into diapause. Read More

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Current and promising therapies in autosomal recessive ataxias.

CNS Neurol Disord Drug Targets 2018 Apr 18. Epub 2018 Apr 18.

Laval University and CHU de Quebec - Laval University, Axe neurosciences - Department of Medicine, Faculty of Medicine Quebec, Quebec. Canada.

Background & Objective: Ataxia is clinically characterized by unsteady gait and imbalance. Cerebellar disorders may arise from many causes such as metabolic diseases, stroke or genetic mutations. The genetic causes are classified by mode of inheritance and include autosomal dominant, X-linked and autosomal recessive ataxias. Read More

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April 2018
1 Read

High-content screen for modifiers of Niemann-Pick type C disease in patient cells.

Hum Mol Genet 2018 Jun;27(12):2101-2112

Conrad Prebys Center for Chemical Genomics, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.

Niemann-Pick type C (NPC) disease is a rare lysosomal storage disease caused primarily by mutations in NPC1. NPC1 encodes the lysosomal cholesterol transport protein NPC1. The most common NPC1 mutation is a missense mutation (NPC1I1061T) that causes misfolding and rapid degradation of mutant protein in the endoplasmic reticulum. Read More

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June 2018
3 Reads

Attenuation of the Niemann-Pick type C2 disease phenotype by intracisternal administration of an AAVrh.10 vector expressing Npc2.

Exp Neurol 2018 Aug 12;306:22-33. Epub 2018 Apr 12.

Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, United States. Electronic address:

Niemann-Pick type C2 (NPC2) disease is a rare, neurodegenerative disorder caused by mutations in the NPC2 gene, leading to lysosomal accumulation of unesterified cholesterol and other lipids. It is characterized by hepatosplenomegaly, liver dysfunction and severe neurological manifestations, resulting in early death. There is no effective therapy for NPC2 disease. Read More

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August 2018
4 Reads

Identification of unusual oxysterols and bile acids with 7-oxo or 3β,5α,6β-trihydroxy functions in human plasma by charge-tagging mass spectrometry with multistage fragmentation.

J Lipid Res 2018 Jun 6;59(6):1058-1070. Epub 2018 Apr 6.

Swansea University Medical School, Swansea SA2 8PP, Wales, United Kingdom

7-Oxocholesterol (7-OC), 5,6-epoxycholesterol (5,6-EC), and its hydrolysis product cholestane-3β,5α,6β-triol (3β,5α,6β-triol) are normally minor oxysterols in human samples; however, in disease, their levels may be greatly elevated. This is the case in plasma from patients suffering from some lysosomal storage disorders, e.g. Read More

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June 2018
4 Reads

Consensus clinical management guidelines for Niemann-Pick disease type C.

Orphanet J Rare Dis 2018 Apr 6;13(1):50. Epub 2018 Apr 6.

Mayo 1290 Clinic Department of Pediatric and Adolescent Medicine, Minnesota, USA.

Niemann-Pick Type C (NPC) is a progressive and life limiting autosomal recessive disorder caused by mutations in either the NPC1 or NPC2 gene. Mutations in these genes are associated with abnormal endosomal-lysosomal trafficking, resulting in the accumulation of multiple tissue specific lipids in the lysosomes. The clinical spectrum of NPC disease ranges from a neonatal rapidly progressive fatal disorder to an adult-onset chronic neurodegenerative disease. Read More

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April 2018
2 Reads

Microglia activation in Niemann-Pick disease, type C1 is amendable to therapeutic intervention.

Hum Mol Genet 2018 Jun;27(12):2076-2089

Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, , Bethesda, MD 20879, USA.

Niemann-Pick disease, type C1 (NPC1) is a neurodegenerative disorder with limited treatment options. NPC1 is associated with neuroinflammation; however, attempts to therapeutically target neuroinflammation in NPC1 have had mixed success. We show here that NPC1 neuroinflammation is characterized by an atypical microglia activation phenotype. Read More

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June 2018
2 Reads

Evaluation of Two Liver Treatment Strategies in a Mouse Model of Niemann-Pick-Disease Type C1.

Int J Mol Sci 2018 Mar 24;19(4). Epub 2018 Mar 24.

Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18057 Rostock, Germany.

Niemann-Pick-disease type C1 (NPC1) is an autosomal-recessive cholesterol-storage disorder. Besides other symptoms, NPC1 patients develop liver dysfunction and hepatosplenomegaly. The mechanisms of hepatomegaly and alterations of lipid metabolism-related genes in NPC1 disease are still poorly understood. Read More

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March 2018
3 Reads

Niemann-Pick C2 protein regulates sterol transport between plasma membrane and late endosomes in human fibroblasts.

Chem Phys Lipids 2018 Jul 23;213:48-61. Epub 2018 Mar 23.

Department of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, DK-5230 Odense M, Denmark. Electronic address:

Niemann-Pick disease type C2 is a lipid storage disorder in which mutations in the NPC2 protein cause accumulation of lipoprotein-derived cholesterol in late endosomes and lysosomes (LE/LYSs). Whether cholesterol delivered by other means to NPC2 deficient cells also accumulates in LE/LYSs is currently unknown. We show that the close cholesterol analog dehydroergosterol (DHE), when delivered to the plasma membrane (PM) accumulates in LE/LYSs of human fibroblasts lacking functional NPC2. Read More

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July 2018
1 Read

Butyrate from pectin fermentation inhibits intestinal cholesterol absorption and attenuates atherosclerosis in apolipoprotein E-deficient mice.

J Nutr Biochem 2018 Jun 27;56:175-182. Epub 2018 Feb 27.

Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong Province 510080, PR China; Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province 510080, PR China. Electronic address:

Short-chain fatty acids (SCFAs), the major products of dietary fiber fermentation by intestinal microflora, exert beneficial effects on pathogenesis of multiple metabolic diseases. The aim of this study was to determine whether SCFAs from fermentation of pectin (PE), a soluble dietary fiber, prevent the development of atherosclerosis in apolipoprotein E-deficient (apoE) mice. Male apoE mice (8-week-old) were fed a high-fat, high-cholesterol diet (HCD; 21% wt/wt fat, 0. Read More

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June 2018
3 Reads

Large-scale computational drug repositioning to find treatments for rare diseases.

NPJ Syst Biol Appl 2018 13;4:13. Epub 2018 Mar 13.

1Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 USA.

Rare, or orphan, diseases are conditions afflicting a small subset of people in a population. Although these disorders collectively pose significant health care problems, drug companies require government incentives to develop drugs for rare diseases due to extremely limited individual markets. Computer-aided drug repositioning, i. Read More

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March 2018
1 Read

Contribution of tandem mass spectrometry to the diagnosis of lysosomal storage disorders.

J Inherit Metab Dis 2018 May 19;41(3):457-477. Epub 2018 Mar 19.

Unité Maladies Héréditaires du Métabolisme, Service de Biochimie et Biologie Moléculaire Grand Est, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, 59 boulevard Pinel, 69677, Bron cedex, France.

Tandem mass spectrometry (MS/MS) is a highly sensitive and specific technique. Thanks to the development of triple quadrupole analyzers, it is becoming more widely used in laboratories working in the field of inborn errors of metabolism. We review here the state of the art of this technique applied to the diagnosis of lysosomal storage disorders (LSDs) and how MS/MS has changed the diagnostic rationale in recent years. Read More

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May 2018
2 Reads

Long-term therapy with miglustat and cognitive decline in the adult form of Niemann-Pick disease type C: a case report.

Neurol Sci 2018 Jun 13;39(6):1015-1019. Epub 2018 Mar 13.

Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", Naples, Italy.

Niemann-Pick disease type C (NPC) is a recessive lysosomal lipid storage disorder characterized by central nervous system involvement. Miglustat treatment might improve or stabilize neurological manifestations but there is still limited data on the long-term efficacy. The aim of our study was to report a four-year clinical, neuropsychological and electrophysiological follow-up of two sisters under treatment with miglustat. Read More

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June 2018
5 Reads

Predicting the Binding Mode of 2-Hydroxypropyl-β-cyclodextrin to Cholesterol by Means of the MD Simulation and the 3D-RISM-KH Theory.

J Phys Chem B 2018 May 19;122(21):5716-5725. Epub 2018 Mar 19.

Toyota Physical and Chemical Research Institute , 41-1, Yokomichi , Nagakute , Aichi 480-1192 , Japan.

It has been found that a cyclodextrin derivative, 2-hydroxypropyl-β-cyclodextrin (HPβCD), has reasonable therapeutic effect on Niemann-Pick disease type C, which is caused by abnormal accumulation of unesterified cholesterol and glycolipids in the lysosomes and shortage of esterified cholesterol in other cellular compartments. We study the binding affinity and mode of HPβCD with cholesterol to elucidate the possible mechanism of HPβCD for removing cholesterol from the lysosomes. The dominant binding mode of HPβCD with cholesterol is found based on the molecular dynamics simulation and a statistical mechanics theory of liquids, or the three-dimensional reference interaction site model theory with Kovalenko-Hirata closure relation. Read More

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May 2018
2 Reads

The formation of giant plasma membrane vesicles enable new insights into the regulation of cholesterol efflux.

Exp Cell Res 2018 Apr 6;365(2):194-207. Epub 2018 Mar 6.

Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556-0369, USA. Electronic address:

Aberrant cellular cholesterol accumulation contributes to the pathophysiology of many diseases including neurodegenerative disorders such as Niemann-Pick Type C (NPC) and Alzheimer's Disease. Many aspects of cholesterol efflux from cells remain elusive. Here we describe the utility of cholesterol-rich giant plasma membrane vesicles (GPMVs) as a means to monitor cholesterol that is translocated to the plasma membrane for secretion. Read More

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April 2018
1 Read

Niemann-Pick type C2 protein supplementation in experimental non-alcoholic fatty liver disease.

PLoS One 2018 9;13(3):e0192728. Epub 2018 Mar 9.

Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.

Background And Aims: Hepatic cholesterol deposition drives inflammation and fibrosis in non-alcoholic steatohepatitis (NASH). The Niemann-Pick type C2 (NPC2) protein plays an important role in regulating intracellular cholesterol trafficking and homeostasis. We hypothesized that intravenous NPC2 supplementation reduces cholesterol accumulation, hepatic inflammation and fibrogenesis in a nutritional NASH rat model. Read More

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June 2018
2 Reads

Live-cell imaging of new polyene sterols for improved analysis of intracellular cholesterol transport.

J Microsc 2018 Jul 8;271(1):36-48. Epub 2018 Mar 8.

Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.

Analysis of intracellular cholesterol transport by fluorescence microscopy requires suitable fluorescent analogues of cholesterol. Most existing cholesterol analogues contain lipophilic dyes which can compromise the sterol properties in membranes. An alternative strategy is to introduce additional double bonds into the sterol ring system resulting in intrinsic fluorescence, while at the same time keeping the cholesterol-like properties of the analogues. Read More

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July 2018
1 Read

Recent neuroimaging, neurophysiological, and neuropathological advances for the understanding of NPC.

F1000Res 2018 15;7:194. Epub 2018 Feb 15.

Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa, 11, 25123 Brescia BS, Italy.

Niemann-Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disorder with extensive biological, molecular, and clinical heterogeneity. Recently, numerous studies have tried to shed light on the pathophysiology of the disease, highlighting possible disease pathways common to other neurodegenerative disorders, such as Alzheimer's disease and frontotemporal dementia, and identifying possible candidate biomarkers for disease staging and response to treatment. Miglustat, which reversibly inhibits glycosphingolipid synthesis, has been licensed in the European Union and elsewhere for the treatment of NPC in both children and adults. Read More

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February 2018
2 Reads

Tolerance of chronic HDACi treatment for neurological, visceral and lung Niemann-Pick Type C disease in mice.

Sci Rep 2018 Mar 1;8(1):3875. Epub 2018 Mar 1.

Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN, 46556, USA.

Histone deacetylase (HDAC) inhibitors are of significant interest as drugs. However, their use to treat neurological disorders has raised concern because HDACs are required for brain function. We have previously shown that a triple combination formulation (TCF) of the pan HDACi vorinostat (Vo), 2-hydroxypropyl-beta-cyclodextrin (HPBCD) and polyethylene glycol (PEG) 400 improves pharmacokinetic exposure and entry of Vo into the brain. Read More

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March 2018
3 Reads

Supramolecular Pharmaceutical Sciences: A Novel Concept Combining Pharmaceutical Sciences and Supramolecular Chemistry with a Focus on Cyclodextrin-Based Supermolecules.

Chem Pharm Bull (Tokyo) 2018 ;66(3):207-216

Graduate School of Pharmaceutical Sciences, Kumamoto University.

Supramolecular chemistry is an extremely useful and important domain for understanding pharmaceutical sciences because various physiological reactions and drug activities are based on supramolecular chemistry. However, it is not a major domain in the pharmaceutical field. In this review, we propose a new concept in pharmaceutical sciences termed "supramolecular pharmaceutical sciences," which combines pharmaceutical sciences and supramolecular chemistry. Read More

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March 2018
6 Reads

The prognostic value of Niemann-Pick C1-like protein 1 and Niemann-Pick disease type C2 in hepatocellular carcinoma.

J Cancer 2018 1;9(3):556-563. Epub 2018 Jan 1.

The Second Department of Liver Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.

Niemann-Pick C1-like 1 (NPC1L1) and Niemann-Pick C2 (NPC2) is a critical mediator of cholesterol absorption. The aim of the present study was to investigate the prognostic value of NPC1L1 and NPC2 in human primary hepatocellular carcinoma (HCC). The expression level of NPC1L1 and NPC2 were evaluated by Immunohistochemistry, Westen blot and Real-time Quantitative PCR. Read More

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January 2018
2 Reads

Niemann-Pick Disease, Type C1 Gene Expression in PBMCs is Associated with Interleukin 10 Serum Concentration: a Case-Control Study.

Clin Lab 2018 Jan;64(1):17-24

Background: Recent studies showed that atherosclerosis is a lysosomal storage disease (LSD) and Niemann-Pick disease type C1 (NPC1) is the most important protein of the lysosomal membrane that is involved in the removal of FC from lysosomes. Whereas several in vitro and in vivo studies have described the crosstalk between lysosomal cholesterol accumulation and increased inflammation, there is no study addressing the correlation between NPC1 gene expression and an anti-inflammatory cytokine, interleukin 10 (IL-10) serum concentration in atherosclerotic patients.

Methods: IL-10 and 25-hydroxyvitamin D serum concentrations were quantified by enzyme-linked immunosorbent assay (ELISA) in atherosclerotic patients (n = 40) and a control group (n = 40). Read More

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January 2018
2 Reads

Metabolic causes of nonimmune hydrops fetalis: A next-generation sequencing panel as a first-line investigation.

Clin Chim Acta 2018 Jun 22;481:1-8. Epub 2018 Feb 22.

Department of Metabolic Biochemistry, Rouen University Hospital, Rouen 76000, France; Normandie Univ, UNIROUEN, CHU Rouen, INSERM U1245, 76000 Rouen, France. Electronic address:

Purposes: Hydrops fetalis is a life-threatening fetal condition, and 85% of all cases are classified as nonimmune hydrops fetalis (NIHF). Up to 15% of NIHF cases may be due to inborn errors of metabolism (IEM), but a large proportion of cases linked to metabolic disorders remains undiagnosed. This lack of diagnosis may be related to the limitations of conventional biological procedures, which involve sequential investigations and require multiple samples and steps. Read More

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June 2018
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Niemann-Pick C2 Proteins: A New Function for an Old Family.

Front Physiol 2018 31;9:52. Epub 2018 Jan 31.

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

Niemann-Pick proteins type C2 (NPC2) are carriers of cholesterol in vertebrates, with a single member in each species. The high sequence conservation between mammals and across vertebrates is related to their common function. In contrast, NPC2 proteins in arthropods have undergone extensive duplication and differentiation, probably under environmental pressure, and are likely to have different functions. Read More

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January 2018
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Duodenal Niemann-Pick C1-like 1 expression was negatively correlated with liver X receptor expression in nonalcoholic fatty liver disease.

Korean J Intern Med 2018 Feb 23. Epub 2018 Feb 23.

College of Pharmacy, The Catholic University of Korea, Bucheon, Korea.

Background/aims: Intestinal cholesterol absorption includes intestinal Niemann-Pick C1-like 1 (NPC1L1) and is an important target pathway in nonalcoholic fatty liver disease (NAFLD). We investigated the expression of NPC1L1 and its correlation with liver X receptor (LXR) expression in peripheral mononuclear (PMN) cells in patients with NAFLD.

Methods: We evaluated intestinal expression of NPC1L1 in 25 NAFLD patients and 28 healthy controls. Read More

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February 2018
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Impact of Reduced Cerebellar EAAT Expression on Purkinje Cell Firing Pattern of NPC1-deficient Mice.

Sci Rep 2018 Feb 20;8(1):3318. Epub 2018 Feb 20.

Albrecht-Kossel-Institute for Neuroregeneration (AKos), University Medicine Rostock, Gehlsheimer Straße 20, D-18147, Rostock, Germany.

Niemann-Pick disease Type C1 (NPC1) is a rare hereditary neurodegenerative disease. NPC1-patients suffer, amongst others, from ataxia, based on a loss of cerebellar Purkinje cells (PCs). Impaired expression/function of excitatory amino acid transporters (EAATs) are suspected of contributing to PC-degeneration in hereditary spinocerebellar ataxias (SCAs). Read More

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February 2018
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Systematic review of psychiatric signs in Niemann-Pick disease type C.

World J Biol Psychiatry 2018 Mar 12:1-13. Epub 2018 Mar 12.

e Royal Melbourne Hospital , Melbourne , Australia.

Objectives: We conducted the first systematic literature review and analysis of psychiatric manifestations in Niemann-Pick disease type C (NPC) to describe: (1) time of occurrence of psychiatric manifestations relative to other disease manifestations; and (2) frequent combinations of psychiatric, neurological and visceral disease manifestations.

Methods: A systematic EMBase literature search was conducted to identify, collate and analyze published data from patients with NPC associated with psychiatric symptoms, published between January 1967 and November 2015.

Results: Of 152 identified publications 40 were included after screening that contained useable data from 58 NPC patients (mean [SD] age at diagnosis of NPC 27. Read More

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March 2018
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