niemann pick diseases

Summary

Summary: A group of diseases marked by autosomal recessive inheritance and accumulation of sphingomyelin in cells of the RETICULOENDOTHELIAL SYSTEM. They are divided into 5 subtypes: A-E. Type A (classic infantile form) is caused by a deficiency of SPHINGOMYELIN PHOSPHODIESTERASE and presents at age 6-12 months with progressive hepatosplenomegaly and neurologic deterioration. Type B (non-neuronopathic form) presents in childhood with hepatosplenomegaly and pulmonary infiltrates. Type C (chronic neuronopathic form) is caused by defective intracellular cholesterol transport and is divided into severe infantile, late infantile, juvenile, and neonatal hepatitis forms. Type D (Nova Scotian Variant) is phenotypically similar to type C. Type E is an adult non-neuronopathic form. (From Menkes, Textbook of Child Neurology, 5th ed, pp101-4)

Top Publications

  1. ncbi Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis
    E D Carstea
    National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    Science 277:228-31. 1997
  2. ncbi Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium
    Emyr Lloyd-Evans
    Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, UK
    Nat Med 14:1247-55. 2008
  3. ncbi Identification of HE1 as the second gene of Niemann-Pick C disease
    S Naureckiene
    Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA
    Science 290:2298-301. 2000
  4. pmc Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids and correct lipid trafficking in Niemann-Pick C cells
    Amit Choudhury
    Department of Biochemistry and Molecular Biology, Thoracic Diseases Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    J Clin Invest 109:1541-50. 2002
  5. ncbi Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene
    S K Loftus
    Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health NIH, Bethesda, MD 20892, USA
    Science 277:232-5. 1997
  6. ncbi Niemann-Pick disease type C
    M T Vanier
    INSERM Unit 189, Lyon Sud Medical School, Oullins and Fondation Gillet Mérieux, Lyon Sud Hospital, Pierre Benite, France
    Clin Genet 64:269-81. 2003
  7. ncbi Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study
    Marc C Patterson
    Department of Neurology and Pediatrics, Columbia University, NY, USA
    Lancet Neurol 6:765-72. 2007
  8. ncbi Mechanisms and consequences of impaired lipid trafficking in Niemann-Pick type C1-deficient mammalian cells
    Barbara Karten
    Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada
    Biochim Biophys Acta 1791:659-70. 2009
  9. pmc Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1-/- mouse
    Benny Liu
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 106:2377-82. 2009
  10. ncbi Lipid changes in Niemann-Pick disease type C brain: personal experience and review of the literature
    M T Vanier
    INSERM Unit 189, Department of Biochemistry, Lyon Sud School of Medicine, Oullins, France
    Neurochem Res 24:481-9. 1999

Detail Information

Publications203 found, 100 shown here

  1. ncbi Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis
    E D Carstea
    National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    Science 277:228-31. 1997
    ....
  2. ncbi Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium
    Emyr Lloyd-Evans
    Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, UK
    Nat Med 14:1247-55. 2008
    ..This unique calcium phenotype represents a new target for therapeutic intervention, as elevation of cytosolic calcium with curcumin normalized NPC1 disease cellular phenotypes and prolonged survival of the NPC1 mouse...
  3. ncbi Identification of HE1 as the second gene of Niemann-Pick C disease
    S Naureckiene
    Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA
    Science 290:2298-301. 2000
    ..3, were found in NP-C2 patients but not in controls. Treatment of NP-C2 fibroblasts with exogenous recombinant HE1 protein ameliorated lysosomal accumulation of low density lipoprotein-derived cholesterol...
  4. pmc Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids and correct lipid trafficking in Niemann-Pick C cells
    Amit Choudhury
    Department of Biochemistry and Molecular Biology, Thoracic Diseases Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    J Clin Invest 109:1541-50. 2002
    ..Our results demonstrate a role for Rab7 and Rab9 in the Golgi targeting of glycosphingolipids and suggest a new therapeutic approach for restoring normal lipid trafficking in NP-C cells...
  5. ncbi Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene
    S K Loftus
    Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health NIH, Bethesda, MD 20892, USA
    Science 277:232-5. 1997
    ..The mouse model may provide an important resource for studying the role of NPC1 in cholesterol homeostasis and neurodegeneration and for assessing the efficacy of new drugs for NP-C disease...
  6. ncbi Niemann-Pick disease type C
    M T Vanier
    INSERM Unit 189, Lyon Sud Medical School, Oullins and Fondation Gillet Mérieux, Lyon Sud Hospital, Pierre Benite, France
    Clin Genet 64:269-81. 2003
    ..These studies, conducted in various models, should ultimately lead to a better understanding of the pathophysiology of NPC and new therapeutic approaches...
  7. ncbi Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study
    Marc C Patterson
    Department of Neurology and Pediatrics, Columbia University, NY, USA
    Lancet Neurol 6:765-72. 2007
    ..Miglustat is able to cross the blood-brain barrier, and is thus a potential therapy for neurological diseases. We aimed to establish the effect of miglustat on several markers of NPC severity...
  8. ncbi Mechanisms and consequences of impaired lipid trafficking in Niemann-Pick type C1-deficient mammalian cells
    Barbara Karten
    Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada
    Biochim Biophys Acta 1791:659-70. 2009
    ..Currently, the most promising approach for extending life-span and improving the quality of life for NPC patients is a combination of several treatments each of which individually modestly slows disease progression...
  9. pmc Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1-/- mouse
    Benny Liu
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 106:2377-82. 2009
    ..These findings suggest that CYCLO acutely reverses the lysosomal transport defect seen in NPC disease...
  10. ncbi Lipid changes in Niemann-Pick disease type C brain: personal experience and review of the literature
    M T Vanier
    INSERM Unit 189, Department of Biochemistry, Lyon Sud School of Medicine, Oullins, France
    Neurochem Res 24:481-9. 1999
    ....
  11. pmc Dynamic movements of organelles containing Niemann-Pick C1 protein: NPC1 involvement in late endocytic events
    D C Ko
    Departments of Developmental Biology and Genetics, Howard Hughes Medical Institute, Beckman Center B300, Stanford University School of Medicine, Stanford, California 94305, USA
    Mol Biol Cell 12:601-14. 2001
    ..We conclude that NPC1 protein promotes the creation and/or movement of particular late endosomes, which rapidly transport materials to and from the cell periphery...
  12. pmc Astrocyte-only Npc1 reduces neuronal cholesterol and triples life span of Npc1-/- mice
    Min Zhang
    Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
    J Neurosci Res 86:2848-56. 2008
    ..We conclude that neurodegeneration of Npc1(-/-) mice is greatly affected by the loss of fibrillary astrocyte function...
  13. ncbi Neuropsychological profile of adult patients with Niemann-Pick C1 (NPC1) mutations
    B Klarner
    Institute for Psychogerontology, University of Erlangen Nuremberg, Erlangen, Germany
    J Inherit Metab Dis 30:60-7. 2007
    ..The series of tests used here could be supplemented by the severe impairment battery and Raven matrices tests for patients with advanced disease...
  14. ncbi Cholesterol accumulation in NPC1-deficient neurons is ganglioside dependent
    MARJORIE C GONDRE-LEWIS
    Sidney Weisner Laboratory of Genetic Neurological Disease, Department of Neuroscience, Rose F Kennedy Center for Research in Mental Retardation and Human Development, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Curr Biol 13:1324-9. 2003
    ....
  15. ncbi The neuropsychiatry of Niemann-Pick type C disease in adulthood
    Mark Walterfang
    Neuropsychiatry Unit, Level 2, John Cade Building, Royal Melbourne Hospital, Melbourne 3050, Australia
    J Neuropsychiatry Clin Neurosci 18:158-70. 2006
    ....
  16. ncbi The natural history of Niemann-Pick disease type C in the UK
    J Imrie
    Willink Biochemical Genetics Unit, Royal Manchester Children s Hospital, Manchester, UK
    J Inherit Metab Dis 30:51-9. 2007
    ....
  17. ncbi Cellular mechanism of U18666A-mediated apoptosis in cultured murine cortical neurons: bridging Niemann-Pick disease type C and Alzheimer's disease
    Chor Hui Vivien Koh
    Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore
    Cell Signal 18:1844-53. 2006
    ....
  18. ncbi Neurons in Niemann-Pick disease type C accumulate gangliosides as well as unesterified cholesterol and undergo dendritic and axonal alterations
    M Zervas
    Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Neuropathol Exp Neurol 60:49-64. 2001
    ..These studies suggest that the homeostatic regulation of gangliosides and cholesterol in neurons is mediated by NPC1 and that perturbations in this mechanism cause a complex neuronal storage disorder...
  19. pmc Niemann-Pick C variant detection by altered sphingolipid trafficking and correlation with mutations within a specific domain of NPC1
    X Sun
    Thoracic Diseases Research Unit, Department of Biochemistry and Molecular Biology, Mayo Clinic and Foundation, Rochester, MN 55905, USA
    Am J Hum Genet 68:1361-72. 2001
    ..Our findings should be useful for the detection of NPC variants and also may provide significant new insight regarding NPC1 genotype/phenotype correlations...
  20. ncbi Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease
    K Horinouchi
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Nat Genet 10:288-93. 1995
    ..Thus, the ASM deficient mice should be of great value for studying the pathogenesis and treatment of NPD, and for investigations into the role of ASM in signal transduction and apoptosis...
  21. ncbi Long-term miglustat therapy in children with Niemann-Pick disease type C
    Marc C Patterson
    Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Child Neurol 25:300-5. 2010
    ..Miglustat stabilized neurological disease progression in pediatric patients with Niemann-Pick disease type C, with comparable safety and tolerability to that observed in adults and juveniles...
  22. ncbi Niemann-Pick C disease in Spain: clinical spectrum and development of a disability scale
    C Iturriaga
    Servei de Neurologia, Hospital Sant Joan de Deu, Pg Sant Joan de Déu, 2 08950 Esplugues de Llobregat, Barcelona, Spain
    J Neurol Sci 249:1-6. 2006
    ..To describe the clinical evolution of Niemann-Pick C disease to identify possible factors involved in the diagnosis and severity of the disease...
  23. ncbi Natural history of Niemann-Pick disease type C in a multicentre observational retrospective cohort study
    J E Wraith
    Royal Manchester Children s Hospital, Manchester, UK
    Mol Genet Metab 98:250-4. 2009
    ..In conclusion, our findings showed a progression in all four parameters of the disability scale, representing a continuous, unbroken progression of neurological manifestations...
  24. ncbi Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology
    Thomas Kirkegaard
    Apoptosis Department and Centre for Genotoxic Stress Research, Institute of Cancer Biology, Danish Cancer Society, DK 2100 Copenhagen, Denmark
    Nature 463:549-53. 2010
    ..Taken together, these data open exciting possibilities for the development of new treatments for lysosomal storage disorders and cancer with compounds that enter the lysosomal lumen by the endocytic delivery pathway...
  25. ncbi Intracellular trafficking of Niemann-Pick C proteins 1 and 2: obligate components of subcellular lipid transport
    Laura Liscum
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    Biochim Biophys Acta 1685:22-7. 2004
    ..We propose that the intracellular trafficking patterns of these proteins will provide clues about their function...
  26. ncbi Miglustat in patients with Niemann-Pick disease Type C (NP-C): a multicenter observational retrospective cohort study
    M Pineda
    Hospital Sant Joan de Deu, Barcelona, Spain
    Mol Genet Metab 98:243-9. 2009
    ..Overall, these data support previous clinical trial findings indicating clinically relevant beneficial effects of miglustat on neurological disease progression in patients with NP-C...
  27. ncbi Respiratory disease in Niemann-Pick type C2 is caused by pulmonary alveolar proteinosis
    M Griese
    Dr von Haunersches Kinderspital, University of Munich, Munich, Germany
    Clin Genet 77:119-30. 2010
    ..Our data indicate that respiratory distress in NPC2 disease is associated with a loss of normal NPC2 protein expression in alveolar macrophages and the accumulation of functionally inactive surfactant rich in cholesterol...
  28. pmc Cholesterol accumulation is associated with lysosomal dysfunction and autophagic stress in Npc1 -/- mouse brain
    Guanghong Liao
    Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766 1854, USA
    Am J Pathol 171:962-75. 2007
    ..These results provide strong evidence that cholesterol accumulation-induced changes in autophagy-lysosome function are closely associated with neurodegeneration in NPC...
  29. ncbi The National Niemann-Pick C1 disease database: report of clinical features and health problems
    William S Garver
    Department of Pediatrics, Arizona Health Sciences Center, The University of Arizona, Tucson, Arizona 85724 5073, and Children s Hospital of Pittsburgh, PA, USA
    Am J Med Genet A 143:1204-11. 2007
    ..Together, these findings confirm and extend previous reports investigating the clinical features associated with NPC1 disease...
  30. pmc Niemann-Pick disease type C: spectrum of HE1 mutations and genotype/phenotype correlations in the NPC2 group
    G Millat
    INSERM Unit 189, Lyon Sud Medical School, Oullins, France
    Am J Hum Genet 69:1013-21. 2001
    ..This mutation generated multiple transcripts, including a minute proportion of normally spliced RNA, which may explain the milder phenotype...
  31. ncbi Identification of 58 novel mutations in Niemann-Pick disease type C: correlation with biochemical phenotype and importance of PTC1-like domains in NPC1
    Walter D Park
    Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    Hum Mutat 22:313-25. 2003
    ..This raises the possibilities of an additional NPC complementation group(s) or non-specificity of the biochemical testing for NPC. These caveats must be considered when offering mutation testing as a clinical service...
  32. ncbi Topological analysis of Niemann-Pick C1 protein reveals that the membrane orientation of the putative sterol-sensing domain is identical to those of 3-hydroxy-3-methylglutaryl-CoA reductase and sterol regulatory element binding protein cleavage-activating
    J P Davies
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 275:24367-74. 2000
    ..Furthermore, our data show that the putative SSD of NPC1 is oriented in the same manner as those of HMG-R and SCAP, providing strong evidence that this domain is functionally important...
  33. ncbi Saccades in adult Niemann-Pick disease type C reflect frontal, brainstem, and biochemical deficits
    L A Abel
    Department of Optometry and Vision Sciences, University of Melbourne, Parkville, Australia
    Neurology 72:1083-6. 2009
    ..No study has examined the frontally driven volitional control of saccadic eye movements in NPC...
  34. ncbi Clinical experience with miglustat therapy in pediatric patients with Niemann-Pick disease type C: a case series
    M Pineda
    Department of Pediatric Neurology, Hospital Sant Joan de Deu, Barcelona, Spain
    Mol Genet Metab 99:358-66. 2010
    ..Overall, miglustat appeared to stabilize neurological status in juvenile-onset NP-C patients, but therapeutic benefits appeared smaller among younger patients who were at a more advanced stage of disease at baseline...
  35. ncbi Niemann-Pick C disease: use of denaturing high performance liquid chromatography for the detection of NPC1 and NPC2 genetic variations and impact on management of patients and families
    Gilles Millat
    Inserm and Fondation Gillet Mérieux, Lyon Sud Hospital, 69310 Pierre Benite, France
    Mol Genet Metab 86:220-32. 2005
    ..Among the mutations identified, 29 were novel, including two of the NPC2 gene. We conclude that DHPLC is a rapid, low-cost, highly accurate, and efficient technique for the detection of NPC genetic variants...
  36. ncbi Imatinib therapy blocks cerebellar apoptosis and improves neurological symptoms in a mouse model of Niemann-Pick type C disease
    Alejandra R Alvarez
    Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Alameda 340, Casilla 114 D, Santiago, Chile
    FASEB J 22:3617-27. 2008
    ....
  37. ncbi The adult form of Niemann-Pick disease type C
    Mathieu Sévin
    Assistance Publique Hopitaux de Paris, Fédération des Maladies du Système Nerveux, Paris, France
    Brain 130:120-33. 2007
    ....
  38. pmc Structural basis of sterol binding by NPC2, a lysosomal protein deficient in Niemann-Pick type C2 disease
    Sujuan Xu
    Center for Advanced Biotechnology and Medicine, Department of Biochemistry, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    J Biol Chem 282:23525-31. 2007
    ..The NPC2 structures provide evidence of a malleable binding site, consistent with the previously documented broad range of sterol ligand specificity...
  39. ncbi Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis
    P Santana
    Laboratory of Signal Transduction, Memorial Sloan Kettering Cancer Center New York, New York 10021, USA
    Cell 86:189-99. 1996
    ..These genetic models provide definitive evidence for the involvement of acid sphingomyelinase in one form of stress-induced apoptosis...
  40. pmc Cyclodextrin overcomes deficient lysosome-to-endoplasmic reticulum transport of cholesterol in Niemann-Pick type C cells
    Lina Abi-Mosleh
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9046, USA
    Proc Natl Acad Sci U S A 106:19316-21. 2009
    ..The buildup of cholesteryl esters in the cytosol is expected to be much less toxic than the buildup of free cholesterol in the lysosomes of patients with mutations in NPC1 or NPC2...
  41. pmc NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes
    Rodney E Infante
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    Proc Natl Acad Sci U S A 105:15287-92. 2008
    ..These findings may explain how mutations in either protein can produce a similar clinical phenotype...
  42. pmc Niemann-Pick type C disease in a 68-year-old patient
    G Trendelenburg
    J Neurol Neurosurg Psychiatry 77:997-8. 2006
  43. ncbi Niemann-Pick type C disease in two affected sisters: ocular motor recordings and brain-stem neuropathology
    David Solomon
    Department of Neurology, Johns Hopkins University, Pathology 2 210, 600 N Wolfe Street, Baltimore, MD 21287, USA
    Ann N Y Acad Sci 1039:436-45. 2005
    ..These neuropathologic findings correlate well with our current understanding of the anatomy and physiology of the supranuclear control of vertical gaze...
  44. ncbi Trafficking defects in endogenously synthesized cholesterol in fibroblasts, macrophages, hepatocytes, and glial cells from Niemann-Pick type C1 mice
    Patrick C Reid
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    J Lipid Res 44:1010-9. 2003
    ..Our findings suggest that endoCHOL may contribute significantly to the overall cholesterol accumulation observed in selective tissues affected by Niemann-Pick type C disease...
  45. ncbi Mutation analysis of feline Niemann-Pick C1 disease
    Kyra L Somers
    Colorado State University, Fort Collins, CO, USA
    Mol Genet Metab 79:99-103. 2003
    ..The human cDNA sequence predicts a 1278aa protein with a lysosomal targeting sequence, several trans-membrane domains and extensive homology with other known mediators of cholesterol homeostasis...
  46. pmc Intracellular accumulation of amyloidogenic fragments of amyloid-beta precursor protein in neurons with Niemann-Pick type C defects is associated with endosomal abnormalities
    Lee Way Jin
    Department of Pathology, University of Washington, Seattle, Washington 98104 2499, USA
    Am J Pathol 164:975-85. 2004
    ..Our results suggest that endosomal abnormalities related to abnormal lipid trafficking in NPC may contribute to abnormal APP processing and Abeta42/C99/APP-CTF deposition...
  47. ncbi A novel cholesterol stain reveals early neuronal cholesterol accumulation in the Niemann-Pick type C1 mouse brain
    Patrick C Reid
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    J Lipid Res 45:582-91. 2004
    ....
  48. ncbi 24 month-treatment with miglustat of three patients with Niemann-Pick disease type C: follow up using brain spectroscopy
    Damien Galanaud
    Department of Neuroradiology and Center for NeuroImaging Research CENIR, Pitie Salpetriere Hospital, Assistance Publique Hopitaux de Paris, France
    Mol Genet Metab 96:55-8. 2009
    ....
  49. ncbi Dynamics of lysosomal cholesterol in Niemann-Pick type C and normal human fibroblasts
    Yvonne Lange
    Department of Pathology, Rush Presbyterian St Luke s Medical Center, 1653 W Congress Parkway, Chicago, IL 60612, USA
    J Lipid Res 43:198-204. 2002
    ..We conclude that the large pool of endolysosomal cholesterol in NPC and amphiphile-treated fibroblasts is dynamic and that its turnover, as in normal cells, is dependent on microtubules...
  50. ncbi Cholesterol accumulates in cell bodies, but is decreased in distal axons, of Niemann-Pick C1-deficient neurons
    Barbara Karten
    Canadian Institutes of Health Research Group on the Molecular and Cell Biology of Lipids and Departments of Medicine, Biochemistry and Cell Biology, University of Alberta, Edmonton, Alberta, Canada
    J Neurochem 83:1154-63. 2002
    ..The altered cholesterol distribution between cell bodies and axons suggests that transport of cholesterol, particularly that synthesized endogenously, from cell bodies to distal axons is impaired in NPC1-deficient neurons...
  51. ncbi Genetic variations and treatments that affect the lifespan of the NPC1 mouse
    Benny Liu
    Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX 75390 9151, USA
    J Lipid Res 49:663-9. 2008
    ..It is currently not clear which of these effects is nonspecific or which might relate directly to the molecular defect present in the NPC1 syndrome...
  52. pmc Endogenous and synthetic neurosteroids in treatment of Niemann-Pick Type C disease
    Synthia H Mellon
    Department of Obstetrics, Gynecology and Reproductive Sciences, The Center for Reproductive Sciences, University of California, San Francisco, CA 94143, USA
    Brain Res Rev 57:410-20. 2008
    ..These animal models further establish the wide range of functions of these compounds, which may ultimately be useful for treatment of human diseases...
  53. pmc 2-hydroxypropyl-beta-cyclodextrin raises hearing threshold in normal cats and in cats with Niemann-Pick type C disease
    Sarah Ward
    Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Pediatr Res 68:52-6. 2010
    ..These studies are the first to describe a specific negative effect of HPbetaCD on the auditory system and suggest the need for auditory testing in patients receiving similar doses of HPbetaCD...
  54. pmc Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression
    Cristin D Davidson
    Dominick P Purpura Department of Neuroscience, Rose F Kennedy Center for Research in Mental Retardation and Human Development, Albert Einstein College of Medicine, Bronx, New York, United States of America
    PLoS ONE 4:e6951. 2009
    ..This finding suggested that administration of CD alone, but with greater frequency, might provide additional benefit...
  55. ncbi Lipids on trial: the search for the offending metabolite in Niemann-Pick type C disease
    Emyr Lloyd-Evans
    Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK
    Traffic 11:419-28. 2010
    ..We review the potential role of each of the individual storage lipids in initiating the pathogenic cascade and propose a model of NPC1 and NPC2 function based on the current knowledge...
  56. pmc Endocytosis of beta-cyclodextrins is responsible for cholesterol reduction in Niemann-Pick type C mutant cells
    Anton I Rosenbaum
    Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 107:5477-82. 2010
    ..These findings suggest that cyclodextrin-mediated enhanced cholesterol transport from the endocytic system can reduce cholesterol accumulation in cells with defects in either NPC1 or NPC2...
  57. ncbi Molecular analysis of NPC1 and NPC2 gene in 34 Niemann-Pick C Italian patients: identification and structural modeling of novel mutations
    Tatiana Fancello
    Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, Modena, Italy
    Neurogenetics 10:229-39. 2009
    ..Moreover, the effects of the missense mutations (p.Y634C, p.S636F, p.L648H, and p.V780G) affecting the sterol-sensing domain (SSD) were evaluated by docking simulation between the atomic coordinates of SSD model and cholesterol...
  58. ncbi Critical assessment of chitotriosidase analysis in the rational laboratory diagnosis of children with Gaucher disease and Niemann-Pick disease type A/B and C
    Markus Ries
    Center for Lysosomal Storage Disorders, Children s Hospital, University of Mainz, Mainz, Germany
    J Inherit Metab Dis 29:647-52. 2006
    ..We conclude that, in the above setting, the degree of elevation of chitotriosidase activity can be applied to increase the likelihood of GD, SMD, or NPC and guide the choice of the appropriate confirmatory assay...
  59. ncbi Niemann-Pick type C disease: NPC1 mutations associated with severe and mild cellular cholesterol trafficking alterations
    I Ribeiro
    Genetic Neurobiology, IBMC University of Porto, 4150 180 Porto, Portugal
    Hum Genet 109:24-32. 2001
    ....
  60. pmc Niemann-Pick C1 disease: correlations between NPC1 mutations, levels of NPC1 protein, and phenotypes emphasize the functional significance of the putative sterol-sensing domain and of the cysteine-rich luminal loop
    G Millat
    INSERM Unit 189, Lyon Sud Medical School, Oullins, France
    Am J Hum Genet 68:1373-85. 2001
    ....
  61. pmc Isolated splenomegaly as the presenting feature of Niemann-Pick disease type C
    J Imrie
    Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester M27 4HA, UK
    Arch Dis Child 84:427-9. 2001
    ..If the diagnosis is not considered and established, the family are at risk of having further affected children. Investigation of patients with isolated splenomegaly is not complete until NPC has been excluded...
  62. pmc Cessation of rapid late endosomal tubulovesicular trafficking in Niemann-Pick type C1 disease
    M Zhang
    Lipid Cell Biology Section and Cell Biochemistry Section, National Institute of Diabetes and Digestive and Kidney Diseases, and Developmental and Metabolic Neurology Branch, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 98:4466-71. 2001
    ..We conclude that the neuropathology and cellular lysosomal lipid accumulation in NPC1 disease results, at least in part, from striking defects in late endosomal tubulovesicular trafficking...
  63. pmc Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients
    Laura Rodríguez-Pascau
    Departament de Genetica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
    Hum Mutat 30:1117-22. 2009
    ..This study is the first exhaustive mutational analysis of Spanish Niemann-Pick A/B disease patients...
  64. ncbi Recent advances in elucidating Niemann-Pick C disease
    M T Vanier
    INSERM Unit 189, Lyon Sud Medical School, Oullins, France
    Brain Pathol 8:163-74. 1998
    ..The murine cDNA and the npc(nih) mutation have been characterized. Described homologies of the NPC1 protein are in line with its putative involvement in cellular cholesterol traffic...
  65. ncbi Niemann-Pick C disease: functional characterization of three NPC2 mutations and clinical and molecular update on patients with NPC2
    L Verot
    INSERM, Unit 820, Métabolomique et Maladies Métaboliques, Lyon F 69372, France
    Clin Genet 71:320-30. 2007
    ..Characterization of more naturally occurring NPC2 mutations may help to dissect further the functional domains of the protein...
  66. pmc Mutations in NPC1 highlight a conserved NPC1-specific cysteine-rich domain
    W L Greer
    Department of Pathology, Division of Molecular Pathology and Molecular Genetics, Dalhousie University, Halifax, Nova Scotia, Canada
    Am J Hum Genet 65:1252-60. 1999
    ..That 7 of a total of 13 NPC1 missense mutations are concentrated in this single Npc1-specific domain suggests that integrity of this region is particularly critical for normal functioning of the protein...
  67. ncbi Consequences of NPC1 and NPC2 loss of function in mammalian neurons
    Steven U Walkley
    Sidney Weisner Laboratory of Genetic Neurological Disease Department of Neuroscience, Rose F Kennedy Center for Research in Mental Retardation and Human Development, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Biochim Biophys Acta 1685:48-62. 2004
    ....
  68. pmc The Nova Scotia (type D) form of Niemann-Pick disease is caused by a G3097-->T transversion in NPC1
    W L Greer
    Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia
    Am J Hum Genet 63:52-4. 1998
    ..We have identified a point mutation within this gene (G3097-->T; Gly992-->Trp) that shows complete linkage disequilibrium with NPD, confirming that NPD is an allelic variant of NPC1...
  69. ncbi Niemann-Pick disease type C2 presenting as fatal pulmonary alveolar lipoproteinosis: morphological findings in lung and nervous tissue
    Bjorn Bjurulf
    Department of Pediatrics, Ulleval University Hospital, Oslo, Norway
    Med Sci Monit 14:CS71-5. 2008
    ..The diagnosis of NPC2 was confirmed at postmortem mutational analysis...
  70. ncbi NPC-db, a Niemann-Pick type C disease gene variation database
    Heiko Runz
    Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany
    Hum Mutat 29:345-50. 2008
    ..The user is encouraged to search contents and submit novel information, thereby contributing to generate a valuable open-access tool that will allow a better understanding of the molecular and clinical details of NPC disease...
  71. ncbi Niemann-Pick type C disease: subcellular location and functional characterization of NPC2 proteins with naturally occurring missense mutations
    Karim Chikh
    INSERM Unit 189, Lyon Sud Medical School, Oullins and Fondation Gillet Mérieux, Lyon Sud Hospital, Pierre Benite, France
    Hum Mutat 26:20-8. 2005
    ..Functional characterization of the mutant proteins showed an excellent genotype-phenotype correlation in the three cases for whom a clinical history was available...
  72. ncbi Niemann-Pick disease type C in adults
    J Imrie
    Willink Biochemical Genetics Unit, Royal Manchester Children s Hospital, Manchester M27 4HA, UK
    J Inherit Metab Dis 25:491-500. 2002
    ..The diagnosis should be confirmed in suspected cases by filipin staining of cultured fibroblasts, as well as cholesterol esterification studies and DNA mutation analysis...
  73. ncbi Frontal lobe atrophy due to a mutation in the cholesterol binding protein HE1/NPC2
    Hans H Klünemann
    Department of Psychiatry and Psychotherapy, University of Regensburg School of Medicine, Universitatsstrasse 84, 93053 Regensburg, Germany
    Ann Neurol 52:743-9. 2002
    ..Adult-onset NPC2 with lysosomal storage virtually restricted to neurons represents a novel phenotypic and genotypic variant with diffuse cognitive impairment and focal frontal involvement described for the first time...
  74. pmc Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease
    Natalia Friedland
    Center for Advanced Biotechnology and Medicine, Howard Hughes Medical Institute, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, NJ 08854, USA
    Proc Natl Acad Sci U S A 100:2512-7. 2003
    ..We propose that this region represents the incipient cholesterol-binding site that dilates to accommodate an approximately 740-A(3) cholesterol molecule...
  75. ncbi Autophagy in Niemann-Pick C disease is dependent upon Beclin-1 and responsive to lipid trafficking defects
    Chris D Pacheco
    Neuroscience Program, The University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Hum Mol Genet 16:1495-503. 2007
    ....
  76. ncbi Miglustat in adult and juvenile patients with Niemann-Pick disease type C: long-term data from a clinical trial
    James E Wraith
    Willink Biochemical Genetics Unit, Department of Genetic Medicine, St Mary s Hospital, Manchester, UK
    Mol Genet Metab 99:351-7. 2010
    ..Overall, these data suggest that long-term miglustat therapy stabilizes neurological disease and is well tolerated in adult and juvenile patients with NP-C...
  77. ncbi Beneficial effects of anti-inflammatory therapy in a mouse model of Niemann-Pick disease type C1
    David Smith
    Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK
    Neurobiol Dis 36:242-51. 2009
    ..These data suggest that anti-inflammatory therapy may be a useful adjunctive treatment in the clinical management of NPC1, alone or combined with SRT...
  78. ncbi Treatment of Niemann-Pick disease type C in two children with miglustat: initial responses and maintenance of effects over 1 year
    Y H Chien
    Department of Medical Genetics and Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
    J Inherit Metab Dis 30:826. 2007
    ..We conclude that miglustat can provide therapeutic benefits in CNS symptoms and allows stabilization of systemic disease in childhood-onset NP-C. Further follow-up is crucial to determine the long-term maintenance of these effects...
  79. ncbi NPC1 and NPC2 regulate cellular cholesterol homeostasis through generation of low density lipoprotein cholesterol-derived oxysterols
    Andrey Frolov
    Center for Cardiovascular Research, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri 63110 1010, USA
    J Biol Chem 278:25517-25. 2003
    ..Our findings support a role for NPC1 and NPC2 in the regulation of sterol homeostasis through generation of LDL cholesterol-derived oxysterols and have important implications for the treatment of NPC disease...
  80. ncbi Patterned Purkinje cell degeneration in mouse models of Niemann-Pick type C disease
    Justyna R Sarna
    Department of Cell Biology and Anatomy, and Genes and Development Research Group, Faculty of Medicine, The University of Calgary, Alberta T2N 4N1, Canada
    J Comp Neurol 456:279-91. 2003
    ..The pattern of cell death thus reflects the fundamental compartmentation of the cerebellum into zones and stripes...
  81. ncbi Cholesterol is sequestered in the brains of mice with Niemann-Pick type C disease but turnover is increased
    C Xie
    Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas 75390 8887, USA
    J Neuropathol Exp Neurol 59:1106-17. 2000
    ..Thus, the cholesterol sequestration seen in every organ in NPC disease also occurs in cells of the CNS and may be etiologically related to the neurodegeneration...
  82. pmc Binding between the Niemann-Pick C1 protein and a photoactivatable cholesterol analog requires a functional sterol-sensing domain
    Nobutaka Ohgami
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Proc Natl Acad Sci U S A 101:12473-8. 2004
    ..Overall, the results demonstrate that there is direct binding between NPC1 and azocholestanol; the binding does not require NPC2 but requires a functional SSD within NPC1...
  83. ncbi Acid sphingomyelinase, cell membranes and human disease: lessons from Niemann-Pick disease
    Edward H Schuchman
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, Icahn Medical Institute, New York, NY 10029, USA
    FEBS Lett 584:1895-900. 2010
    ..This review will focus on the role of ASM in membrane biology, with a specific emphasis on what a rare genetic disorder (NPD) has taught us about more common events...
  84. pmc The National Niemann-Pick Type C1 Disease Database: correlation of lipid profiles, mutations, and biochemical phenotypes
    William S Garver
    Department of Pediatrics, University of Arizona, Tucson, AZ 85724 5037, USA
    J Lipid Res 51:406-15. 2010
    ..Together, these findings provide novel information regarding the plasma lipoprotein changes and mutations in NPC1 disease, and suggest plasma HDL-C represents a potential biomarker of NPC1 disease severity...
  85. ncbi [Ultrasound echogenic splenic tumors: nodular manifestation of type C Niemann-Pick disease]
    E Frohlich
    Medizinische Klinik I, Krankenanstalten des Landkreises Ludwigsburg
    Ultraschall Med 11:119-22. 1990
    ..Biochemical lipid analysis of the spleen confirmed Type-C Niemann-Pick disease. Niemann-Pick disease and its subtypes are discussed briefly...
  86. ncbi The pathophysiology and mechanisms of NP-C disease
    Stephen L Sturley
    Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032, USA
    Biochim Biophys Acta 1685:83-7. 2004
    ....
  87. ncbi Subclinical course of adult visceral Niemann-Pick type C1 disease. A rare or underdiagnosed disorder?
    L Dvorakova
    Institute of Inherited Metabolic Disorders, Charles University, First Faculty of Medicine and University Hospital, Prague, Czech Republic
    J Inherit Metab Dis 29:591. 2006
    ..Although only three patients have been reported, this (most probably underdiagnosed) form of NPC should be considered in differential diagnosis of isolated hepatosplenomegaly with foam cells in adulthood...
  88. ncbi Cholesterol homeostasis in neurons and glial cells
    Jean E Vance
    Department of Medicine, Canadian Institutes for Health Research, Group on the Molecular and Cell Biology of Lipids, 332 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada T6G 2S2
    Semin Cell Dev Biol 16:193-212. 2005
    ..In addition, the progressive neurodegenerative disorder Niemann-Pick C disease is characterized by defects in intracellular trafficking of cholesterol...
  89. pmc Rab8-dependent recycling promotes endosomal cholesterol removal in normal and sphingolipidosis cells
    Matts D Linder
    Institute of Biomedicine Anatomy, University of Helsinki, FI 00014 Helsinki, Finland
    Mol Biol Cell 18:47-56. 2007
    ..Our findings establish Rab8 as a key component of the regulatory machinery that leads to ABCA1-dependent removal of cholesterol from endocytic circuits...
  90. ncbi Sterol, protein and lipid trafficking in Chinese hamster ovary cells with Niemann-Pick type C1 defect
    Nina H Pipalia
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Traffic 8:130-41. 2007
    ..These data are consistent with multiple trafficking defects in both early and late endosomes in NPC cells...
  91. ncbi Fitting a mathematical model to biological data: intracellular trafficking in Niemann-Pick C disease
    Meryl E Wastney
    Metabolic Modeling Services, Dalesford, Hamilton, New Zealand
    Adv Exp Med Biol 537:63-75. 2003
  92. ncbi Understanding Niemann-Pick type C disease: a fat problem
    Inez Vincent
    Department of Pathology, K078A, University of Washington, Box 357705, 1959 NE Pacific Avenue, Seattle, WA 98195, USA
    Curr Opin Neurol 16:155-61. 2003
    ....
  93. pmc Accumulation of cholera toxin and GM1 ganglioside in the early endosome of Niemann-Pick C1-deficient cells
    Y Sugimoto
    Department of Neurobiology, Tottori University Faculty of Medicine, Yonago 683, Japan
    Proc Natl Acad Sci U S A 98:12391-6. 2001
    ..These results suggest that transport of CT/GM1 complexes from the early endosome to the plasma membrane depends on the function of NPC1, whereas transport to the Golgi apparatus/endoplasmic reticulum does not...
  94. ncbi Presenilin redistribution associated with aberrant cholesterol transport enhances beta-amyloid production in vivo
    Mark Burns
    Center for Dementia Research, Nathan S Kline Institute, Orangeburg, New York 10962, USA
    J Neurosci 23:5645-9. 2003
    ..Our results show that aberrant cholesterol trafficking is associated with the potentiation of APP processing components in vivo, leading to an overall increase in Abeta levels...
  95. ncbi Cyclodextrins in the treatment of a mouse model of Niemann-Pick C disease
    F Camargo
    Steele Memorial Children's Research Center, Department of Pediatrics, The University of Arizona College of Medicine, Tucson 85724, USA
    Life Sci 70:131-42. 2001
    ..Intrathecal delivery of HPBCD by an Alzet osmotic minipump did not improve its efficacy in ameliorating neurological symptoms...
  96. ncbi Glucosylceramidase mass and subcellular localization are modulated by cholesterol in Niemann-Pick disease type C
    Rosa Salvioli
    Department of Hematology, Istituto Superiore Sanita, 00161 Roma, Italy
    J Biol Chem 279:17674-80. 2004
    ..These data show for the first time that the level of cholesterol modulates the interaction of GCase with its protein and lipid activators, namely Sap C and LBPA, regulating the GCase activity and stability...
  97. ncbi Biotinylated theta-toxin derivative as a probe to examine intracellular cholesterol-rich domains in normal and Niemann-Pick type C1 cells
    Shigeki Sugii
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    J Lipid Res 44:1033-41. 2003
    ..Thus, BCtheta is a powerful tool for visually monitoring cholesterol-rich domains inside normal and NPC cells...
  98. pmc Niemann-Pick C1 disease: the I1061T substitution is a frequent mutant allele in patients of Western European descent and correlates with a classic juvenile phenotype
    G Millat
    INSERM 189, Lyon Sud Medical School, Oullins, France
    Am J Hum Genet 65:1321-9. 1999
    ..The mutation was not found (0/40 alleles) in patients with the severe infantile neurological form of the disease. Testing for this mutation therefore has important implications for genetic counseling of families affected by NPC...
  99. ncbi Niemann-pick disease type C in neonatal cholestasis at a North American Center
    Baruch Yerushalmi
    Pediatric Liver Center and Liver Transplantation Program, Department of Pediatrics, University of Colorado School of Medicine and The Children s Hospital, Denver, Colorado 80218, USA
    J Pediatr Gastroenterol Nutr 35:44-50. 2002
    ..To determine the frequency of Niemann-Pick disease type C (NPC) among children being evaluated for neonatal cholestasis during a 2-year period...
  100. ncbi Spiral analysis in Niemann-Pick disease type C
    Annie W Hsu
    Department of Neurology, Clinical Motor Physiology Laboratory, Columbia University Medical Center, New York, New York, USA
    Mov Disord 24:1984-90. 2009
    ..Other features, such as the tightness of loop widths, were normal. Our findings reveal that differing aspects of tremor, Parkinsonism, ataxia, and dystonia are quantifiable in NPC patients...
  101. ncbi Automated microscopy screening for compounds that partially revert cholesterol accumulation in Niemann-Pick C cells
    Nina H Pipalia
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    J Lipid Res 47:284-301. 2006
    ..These compounds are effective at concentrations of 123 nM to 3 microM in reducing the cholesterol accumulation in cells with a NPC1 phenotype...

Research Grants34

  1. Graduate Medical Education in Genetics
    Margaret McGovern; Fiscal Year: 2004
    ..abstract_text> ..
  2. Preclinical development of a gene therapy for Niemann-Pick disease, type A
    Krystof S Bankiewicz; Fiscal Year: 2011
    ..We propose experiments in this application that we believe will form the basis of a major improvement in brain gene therapy in general, and more specifically in the treatment of neurological aspects of LSD's. ..
  3. A LINKAGE STUDY IN FAMILIAL PULMONARY FIBROSIS
    Mark Steele; Fiscal Year: 2004
    ....
  4. Chemical chaperones for Niemann-Pick C disease
    Yiannis Ioannou; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  5. Functional Characterization of the NPC Homologue NPC1L1
    Yiannis Ioannou; Fiscal Year: 2007
    ....
  6. Insulin Resistance and ABCA1 Transporter Function
    WILLIAM GARVER; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  7. NIEMANN-PICK C AND INTRACELLULAR CHOLESTEROL TRANSPORT
    Yiannis Ioannou; Fiscal Year: 2004
    ..abstract_text> ..
  8. The Glycoproteinoses: Second International Workshop on Advances in Pathogenesis a
    STEVEN WALKLEY; Fiscal Year: 2007
    ..Enhancement of research on the glycoproteinoses could provide important breakthroughs for the understanding and treatment of not only these diseases but for all genetic brain disorders. [unreadable] [unreadable] [unreadable]..
  9. GANGLIOSIDES AND DENDRITOGENESIS IN CORTICAL DEVELOPMENT
    STEVEN WALKLEY; Fiscal Year: 2001
    ..The goal of this research proposal is to rigorously test this hypothesis in the normal, developing cerebral cortex using a combination of in vivo and in vitro studies. ..
  10. Analysis of a suppressor of the Niemann-Pick C phenotype
    Laura Liscum; Fiscal Year: 2008
    ..Elucidation of cellular factors responsible for cholesterol clearance from NPC lysosomes will reveal potential therapeutic targets for this devastating neurodegenerative disease. [unreadable] [unreadable]..
  11. NIEMANN-PICK DISEASE
    Melissa Wasserstein; Fiscal Year: 2005
    ..In sum, these studies should provide important diagnostic and therapeutic information to improve the outcome of patients diagnosed with NPD. ..
  12. Neurodegeneration in Niemann-Pick Type C Disease
    Xiaoning Bi; Fiscal Year: 2009
    ..Finally, because microglia activation has also been implicated in the mechanisms underlying several neurodegenerative diseases, our proposal could lead to significant advances in the treatment of these diseases as well. ..
  13. Steroidogenic Acute Regulatory Protein's Role in Libido
    Steven King; Fiscal Year: 2004
    ....
  14. Targeted enzyme delivery systems for treatment of orphan niemann-pick disease
    SILVIA MURO GALINDO; Fiscal Year: 2007
    ..The clinical benefits of this strategy may be extended to other LSDs. [unreadable] [unreadable] [unreadable] [unreadable]..
  15. PHARMACOLOGICAL STUDIES OF HUMAN AND CANINE NARCOLEPSY
    Seiji Nishino; Fiscal Year: 2002
    ....
  16. Role of Histamine in Narcolepsy/EDS Disorders
    Seiji Nishino; Fiscal Year: 2008
    ..As almost nothing is known on the pathophysiology of non- hypocretin deficient hypersomnias, we believe this work to be ideally suited for a small grant application. [unreadable] [unreadable] [unreadable]..
  17. A conditional null mutant of the mouse Npc1 gene
    Andrew Lieberman; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  18. Sterol Sensing and Transport in Model Eukaryote
    STEPHEN STURLEY; Fiscal Year: 2008
    ..We will test the ramifications of overexpression or knockdown of human ARVl in various tissue culture cell models. Lipid efflux to extracellular acceptors will be studied in detail. ..
  19. Role of hypocretin/histamine in Narcolepsy/EDS disorders
    Seiji Nishino; Fiscal Year: 2009
    ..We believe that results from these studies will bring new insights regarding the roles of the hypocretin/histamine interaction in narcolepsy and other EDS disorders and better treatment modalities in humans. ..
  20. TROPHIC MANIPULATIONS OF THE OCULOMOTOR SYSTEM
    Christopher S von Bartheld; Fiscal Year: 2010
    ....
  21. Studies of Prosaposin's Physiologic Role
    Gregory Grabowski; Fiscal Year: 2007
    ..These studies have implications for GSL metabolism, and lysosomal storage disease phenotypic expression and therapy. ..
  22. Use of Hammerhead Ribozymes in Murine Models of Ol
    Gregory Grabowski; Fiscal Year: 2007
    ....
  23. EXPERIMENTAL PATHOLOGY OF DEVELOPING NERVOUS SYSTEM
    Kinuko Suzuki; Fiscal Year: 2004
    ..Therefore, in Aim 5 possible protective role of insulin-like growth factor for neuronal degeneration will be tested by interbreeding NPC mouse with IGF-I transgenic mouse. ..
  24. Function and Signaling Mechanisms of Leptin Receptors
    Joyce Repa; Fiscal Year: 2005
    ..A better understanding of the signal transduction pathway used by leptin may reveal novel strategies to enhance or inhibit leptin's biological activities for therapeutic purposes. ..
  25. LASER SCANNING CONFOCAL MICROSCOPE
    Ralph Nixon; Fiscal Year: 2005
    ....
  26. REGULATION OF REPRODUCTION
    Synthia Mellon; Fiscal Year: 2005
    ..abstract_text> ..
  27. Attenuating sterol synthesis in WT and NPC mice brains
    Ta Yuan Chang; Fiscal Year: 2005
    ..Specific Aim 3: To examine the long-term effect of SSI CP-340868 at 2 different doses on life spans of normal and NPC1 mice. ..
  28. CDP-choline: Mechanisms in Cerebral Ischemia
    RAO ADIBHATLA; Fiscal Year: 2006
    ..Arachidonic acid activates neutral sphingomyelinase, resulting in membrane disintegration. PCCT activity was stimulated by exogenous CDP-choline. Aim 2 will be tested in gerbil transient forebrain ischemia. ..
  29. INBORN ERRORS OF SPHINGOLIPID CATABOLISM
    Gregory Grabowski; Fiscal Year: 2004
    ..abstract_text> ..
  30. ROLE OF SURFACTANT PROTEIN D IN SURFACTANT HOMEOSTASIS
    Machiko Ikegami; Fiscal Year: 2006
    ..The intended studies will provide fundamental insights into the role of SP-D in the protection of the lung, as well as into the basic mechanisms determining surfactant homeostasis. ..
  31. Altered Androgen Receptor Function Due to CAG Expansion
    Andrew Lieberman; Fiscal Year: 2003
    ..Such outcomes will have general impact because this new knowledge will suggest novel targets for the treatment of this and related diseases. ..
  32. MRI, MIT, and MRS of MPS VII and Krabbe Disease
    Charles Vite; Fiscal Year: 2003
    ..x0a; ..
  33. Modifiers of Polyglutamine Toxicity
    Andrew Lieberman; Fiscal Year: 2006
    ..Such outcomes will have general impact by furthering our understanding of disease pathogenesis and by yielding a mouse model that faithfully recapitulates the human disease. [unreadable] [unreadable] [unreadable] [unreadable]..