niemann pick diseases

Summary

Summary: A group of autosomal recessive disorders in which harmful quantities of lipids accumulate in the viscera and the central nervous system. They can be caused by deficiencies of enzyme activities (SPHINGOMYELIN PHOSPHODIESTERASE) or defects in intracellular transport, resulting in the accumulation of SPHINGOMYELINS and CHOLESTEROL. There are various subtypes based on their clinical and genetic differences.

Top Publications

  1. Ioannou Y. Guilty until proven innocent: the case of NPC1 and cholesterol. Trends Biochem Sci. 2005;30:498-505 pubmed
    ..I propose a new hypothesis for the potential action or function of the NPC1 protein in the endosome. In this context, the relationship of NPC2 and NPC1 is also discussed. ..
  2. Jin L, Shie F, Maezawa I, Vincent I, Bird T. Intracellular accumulation of amyloidogenic fragments of amyloid-beta precursor protein in neurons with Niemann-Pick type C defects is associated with endosomal abnormalities. Am J Pathol. 2004;164:975-85 pubmed
    ..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. ..
  3. Imrie J, Galani C, Gairy K, Lock K, Hunsche E. Cost of illness associated with Niemann-Pick disease type C in the UK. J Med Econ. 2009;12:219-29 pubmed publisher
    ..These findings highlight the need for treatments that can slow or stop disease progression in NP-C. ..
  4. Patterson M, Vecchio D, Prady H, Abel L, Wraith J. Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study. Lancet Neurol. 2007;6:765-72 pubmed
    ..Miglustat improves or stabilises several clinically relevant markers of NPC. This is the first agent studied in NPC for which there is both animal and clinical data supporting a disease modifying benefit. ..
  5. Salvioli R, Scarpa S, Ciaffoni F, Tatti M, Ramoni C, Vanier M, et al. Glucosylceramidase mass and subcellular localization are modulated by cholesterol in Niemann-Pick disease type C. J Biol Chem. 2004;279:17674-80 pubmed
    ..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. ..
  6. Runz H, Dolle D, Schlitter A, Zschocke J. NPC-db, a Niemann-Pick type C disease gene variation database. Hum Mutat. 2008;29:345-50 pubmed
    ..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. ..
  7. Yerushalmi B, Sokol R, Narkewicz M, Smith D, Ashmead J, Wenger D. Niemann-pick disease type C in neonatal cholestasis at a North American Center. J Pediatr Gastroenterol Nutr. 2002;35:44-50 pubmed
    ..Electron microscopy and lipid analysis of liver biopsy specimens obtained during the evaluation of neonatal cholestasis may suggest this diagnosis. ..
  8. Friedland N, Liou H, Lobel P, Stock A. Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease. Proc Natl Acad Sci U S A. 2003;100:2512-7 pubmed
    ..We propose that this region represents the incipient cholesterol-binding site that dilates to accommodate an approximately 740-A(3) cholesterol molecule. ..
  9. Imrie J, DasGupta S, Besley G, Harris C, Heptinstall L, Knight S, et al. The natural history of Niemann-Pick disease type C in the UK. J Inherit Metab Dis. 2007;30:51-9 pubmed

More Information

Publications88

  1. Zhang M, Strnatka D, Donohue C, Hallows J, Vincent I, Erickson R. Astrocyte-only Npc1 reduces neuronal cholesterol and triples life span of Npc1-/- mice. J Neurosci Res. 2008;86:2848-56 pubmed publisher
    ..We conclude that neurodegeneration of Npc1(-/-) mice is greatly affected by the loss of fibrillary astrocyte function. ..
  2. Wang M, Franklin V, Sundaram M, Kiss R, Ho K, Gallant M, et al. Differential regulation of ATP binding cassette protein A1 expression and ApoA-I lipidation by Niemann-Pick type C1 in murine hepatocytes and macrophages. J Biol Chem. 2007;282:22525-33 pubmed
    ..Therefore, Abca1 expression is specifically regulated in hepatocytes, where Npc1 activity modulates cathepsin D expression and Abca1 protein translation rate...
  3. Hsu A, Piboolnurak P, Floyd A, Yu Q, Wraith J, Patterson M, et al. Spiral analysis in Niemann-Pick disease type C. Mov Disord. 2009;24:1984-90 pubmed publisher
    ..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. ..
  4. Iturriaga C, Pineda M, Fernández Valero E, Vanier M, Coll M. Niemann-Pick C disease in Spain: clinical spectrum and development of a disability scale. J Neurol Sci. 2006;249:1-6 pubmed
    ..A disability scale could be useful for monitoring evolution, establishing possible phenotypic correlations and evaluating future therapies. ..
  5. Scheel M, Abegg M, Lanyon L, Mattman A, Barton J. Eye movement and diffusion tensor imaging analysis of treatment effects in a Niemann-Pick Type C patient. Mol Genet Metab. 2010;99:291-5 pubmed publisher
    ..This method might be useful in future treatment trials for NPC to assess treatment effects. ..
  6. Ries M, Schaefer E, Lührs T, Mani L, Kuhn J, Vanier M, et al. Critical assessment of chitotriosidase analysis in the rational laboratory diagnosis of children with Gaucher disease and Niemann-Pick disease type A/B and C. J Inherit Metab Dis. 2006;29:647-52 pubmed
    ..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. ..
  7. Smith D, Wallom K, Williams I, Jeyakumar M, Platt F. Beneficial effects of anti-inflammatory therapy in a mouse model of Niemann-Pick disease type C1. Neurobiol Dis. 2009;36:242-51 pubmed publisher
    ..These data suggest that anti-inflammatory therapy may be a useful adjunctive treatment in the clinical management of NPC1, alone or combined with SRT. ..
  8. Davidson C, Ali N, Micsenyi M, Stephney G, Renault S, Dobrenis K, et al. Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression. PLoS ONE. 2009;4:e6951 pubmed publisher
    ..Understanding the mechanism(s) by which CD leads to reduced neuronal storage may provide important new opportunities for treatment of NPC and related neurodegenerative diseases characterized by cholesterol dyshomeostasis. ..
  9. Mukherjee S, Maxfield F. Lipid and cholesterol trafficking in NPC. Biochim Biophys Acta. 2004;1685:28-37 pubmed
    ..We also discuss some potential therapeutic directions being suggested by recent research. ..
  10. Pineda M, Wraith J, Mengel E, Sedel F, Hwu W, Rohrbach M, et al. Miglustat in patients with Niemann-Pick disease Type C (NP-C): a multicenter observational retrospective cohort study. Mol Genet Metab. 2009;98:243-9 pubmed publisher
    ..Overall, these data support previous clinical trial findings indicating clinically relevant beneficial effects of miglustat on neurological disease progression in patients with NP-C. ..
  11. Lloyd Evans E, Morgan A, He X, Smith D, Elliot Smith E, Sillence D, et al. Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat Med. 2008;14:1247-55 pubmed publisher
    ..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. ..
  12. Vanier M, Millat G. Structure and function of the NPC2 protein. Biochim Biophys Acta. 2004;1685:14-21 pubmed
    ..In this model, the activity of NPC1 would depend on that of NPC2. The precise function of the NPC2 protein has, however, not been fully elucidated. ..
  13. Koh C, Cheung N. Cellular mechanism of U18666A-mediated apoptosis in cultured murine cortical neurons: bridging Niemann-Pick disease type C and Alzheimer's disease. Cell Signal. 2006;18:1844-53 pubmed
  14. Liu B, Turley S, Burns D, Miller A, Repa J, Dietschy J. Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1-/- mouse. Proc Natl Acad Sci U S A. 2009;106:2377-82 pubmed publisher
    ..These findings suggest that CYCLO acutely reverses the lysosomal transport defect seen in NPC disease. ..
  15. Klarner B, Klünemann H, Lürding R, Aslanidis C, Rupprecht R. Neuropsychological profile of adult patients with Niemann-Pick C1 (NPC1) mutations. J Inherit Metab Dis. 2007;30:60-7 pubmed
    ..The series of tests used here could be supplemented by the severe impairment battery and Raven matrices tests for patients with advanced disease. ..
  16. Walterfang M, Fietz M, Fahey M, Sullivan D, Leane P, Lubman D, et al. The neuropsychiatry of Niemann-Pick type C disease in adulthood. J Neuropsychiatry Clin Neurosci. 2006;18:158-70 pubmed
  17. Sugii S, Reid P, Ohgami N, Shimada Y, Maue R, Ninomiya H, et al. Biotinylated theta-toxin derivative as a probe to examine intracellular cholesterol-rich domains in normal and Niemann-Pick type C1 cells. J Lipid Res. 2003;44:1033-41 pubmed
    ..Thus, BCtheta is a powerful tool for visually monitoring cholesterol-rich domains inside normal and NPC cells. ..
  18. Chevallier J, Chamoun Z, Jiang G, Prestwich G, Sakai N, Matile S, et al. Lysobisphosphatidic acid controls endosomal cholesterol levels. J Biol Chem. 2008;283:27871-80 pubmed publisher
    ..We conclude that LBPA controls the cholesterol capacity of endosomes...
  19. Chen F, Gordon R, Ioannou Y. NPC1 late endosomes contain elevated levels of non-esterified ('free') fatty acids and an abnormally glycosylated form of the NPC2 protein. Biochem J. 2005;390:549-61 pubmed
    ..These results suggest that the function of the NPC2 protein may be compromised as well in NPC1 endosomes, which might explain the paradoxical phenotypic similarities of the two NPC disease complementation groups...
  20. Trendelenburg G, Vanier M, Maza S, Millat G, Bohner G, Munz D, et al. Niemann-Pick type C disease in a 68-year-old patient. J Neurol Neurosurg Psychiatry. 2006;77:997-8 pubmed
  21. Patterson M, Vecchio D, Jacklin E, Abel L, Chadha Boreham H, Luzy C, et al. Long-term miglustat therapy in children with Niemann-Pick disease type C. J Child Neurol. 2010;25:300-5 pubmed publisher
    ..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. Wraith J, Guffon N, Rohrbach M, Hwu W, Korenke G, Bembi B, et al. Natural history of Niemann-Pick disease type C in a multicentre observational retrospective cohort study. Mol Genet Metab. 2009;98:250-4 pubmed publisher
    ..In conclusion, our findings showed a progression in all four parameters of the disability scale, representing a continuous, unbroken progression of neurological manifestations...
  23. Oyama K, Takahashi T, Shoji Y, Oyamada M, Noguchi A, Tamura H, et al. Niemann-Pick disease type C: cataplexy and hypocretin in cerebrospinal fluid. Tohoku J Exp Med. 2006;209:263-7 pubmed
    ..All of the NPC cases with cataplexy demonstrated low levels of CSF hypocretin-1, confirming the association of reduced CSF hypocretin-1 levels with cataplexy in NPC...
  24. Abel L, Walterfang M, Fietz M, Bowman E, Velakoulis D. Saccades in adult Niemann-Pick disease type C reflect frontal, brainstem, and biochemical deficits. Neurology. 2009;72:1083-6 pubmed publisher
    ..No study has examined the frontally driven volitional control of saccadic eye movements in NPC...
  25. Ribeiro I, Marcao A, Amaral O, Sa Miranda M, Vanier M, Millat G. Niemann-Pick type C disease: NPC1 mutations associated with severe and mild cellular cholesterol trafficking alterations. Hum Genet. 2001;109:24-32 pubmed
  26. Chien Y, Lee N, Tsai L, Huang A, Peng S, Chen S, et al. Treatment of Niemann-Pick disease type C in two children with miglustat: initial responses and maintenance of effects over 1 year. J Inherit Metab Dis. 2007;30:826 pubmed
    ..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...
  27. Millat G, Baïlo N, Molinero S, Rodriguez C, Chikh K, Vanier M. 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. Mol Genet Metab. 2005;86:220-32 pubmed
    ..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...
  28. Infante R, Wang M, Radhakrishnan A, Kwon H, Brown M, Goldstein J. NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes. Proc Natl Acad Sci U S A. 2008;105:15287-92 pubmed publisher
    ..These findings may explain how mutations in either protein can produce a similar clinical phenotype...
  29. te Vruchte D, Lloyd Evans E, Veldman R, Neville D, Dwek R, Platt F, et al. Accumulation of glycosphingolipids in Niemann-Pick C disease disrupts endosomal transport. J Biol Chem. 2004;279:26167-75 pubmed
    ..It is suggested that accumulating GSL is part of a mislocalized membrane microdomain and is responsible for the deficit in endocytic trafficking found in NPC disease...
  30. Ikonen E, Hölttä Vuori M. Cellular pathology of Niemann-Pick type C disease. Semin Cell Dev Biol. 2004;15:445-54 pubmed
    ..The importance of NPC as a model for subcellular lipid imbalance in studying more common diseases, such as Alzheimer's and cardiovascular diseases, is discussed...
  31. Camargo F, Erickson R, Garver W, Hossain G, Carbone P, Heidenreich R, et al. Cyclodextrins in the treatment of a mouse model of Niemann-Pick C disease. Life Sci. 2001;70:131-42 pubmed
    ..Intrathecal delivery of HPBCD by an Alzet osmotic minipump did not improve its efficacy in ameliorating neurological symptoms...
  32. Griffin L, Gong W, Verot L, Mellon S. Niemann-Pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanolone. Nat Med. 2004;10:704-11 pubmed
    ..Earlier administration increases effectiveness of treatment. Decreased production of allopregnanolone apparently contributes to the pathology of NP-C; thus, neurosteroid treatment may be useful in ameliorating progression of the disease...
  33. Kaptzan T, West S, Holicky E, Wheatley C, Marks D, Wang T, et al. Development of a Rab9 transgenic mouse and its ability to increase the lifespan of a murine model of Niemann-Pick type C disease. Am J Pathol. 2009;174:14-20 pubmed publisher
    ..These results demonstrate that Rab9 overexpression has the potential to reduce stored lipids and prolong lifespan in vivo...
  34. Garver W, Francis G, Jelinek D, Shepherd G, Flynn J, Castro G, et al. The National Niemann-Pick C1 disease database: report of clinical features and health problems. Am J Med Genet A. 2007;143A:1204-11 pubmed
    ..Together, these findings confirm and extend previous reports investigating the clinical features associated with NPC1 disease...
  35. Xu S, Benoff B, Liou H, Lobel P, Stock A. Structural basis of sterol binding by NPC2, a lysosomal protein deficient in Niemann-Pick type C2 disease. J Biol Chem. 2007;282:23525-31 pubmed
    ..The NPC2 structures provide evidence of a malleable binding site, consistent with the previously documented broad range of sterol ligand specificity...
  36. Schuchman E. Acid sphingomyelinase, cell membranes and human disease: lessons from Niemann-Pick disease. FEBS Lett. 2010;584:1895-900 pubmed publisher
    ..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...
  37. Rodríguez Pascau L, Gort L, Schuchman E, Vilageliu L, Grinberg D, Chabas A. Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients. Hum Mutat. 2009;30:1117-22 pubmed publisher
    ..This study is the first exhaustive mutational analysis of Spanish Niemann-Pick A/B disease patients...
  38. Reid P, Sugii S, Chang T. Trafficking defects in endogenously synthesized cholesterol in fibroblasts, macrophages, hepatocytes, and glial cells from Niemann-Pick type C1 mice. J Lipid Res. 2003;44:1010-9 pubmed
    ..Our findings suggest that endoCHOL may contribute significantly to the overall cholesterol accumulation observed in selective tissues affected by Niemann-Pick type C disease...
  39. Klünemann H, Elleder M, Kaminski W, Snow K, Peyser J, O Brien J, et al. Frontal lobe atrophy due to a mutation in the cholesterol binding protein HE1/NPC2. Ann Neurol. 2002;52:743-9 pubmed
    ..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...
  40. Vance J, Hayashi H, Karten B. Cholesterol homeostasis in neurons and glial cells. Semin Cell Dev Biol. 2005;16:193-212 pubmed
    ..In addition, the progressive neurodegenerative disorder Niemann-Pick C disease is characterized by defects in intracellular trafficking of cholesterol...
  41. Millat G, Chikh K, Naureckiene S, Sleat D, Fensom A, Higaki K, et al. Niemann-Pick disease type C: spectrum of HE1 mutations and genotype/phenotype correlations in the NPC2 group. Am J Hum Genet. 2001;69:1013-21 pubmed
    ..This mutation generated multiple transcripts, including a minute proportion of normally spliced RNA, which may explain the milder phenotype...
  42. Narita K, Choudhury A, Dobrenis K, Sharma D, Holicky E, Marks D, et al. Protein transduction of Rab9 in Niemann-Pick C cells reduces cholesterol storage. FASEB J. 2005;19:1558-60 pubmed
    ..These observations provide important new information about the correction of membrane traffic in NPC cells by Rab9 overexpression and may lead to new therapeutic approaches for treatment of this disease...
  43. Galanaud D, Tourbah A, Lehericy S, Leveque N, Heron B, Billette De Villemeur T, et al. 24 month-treatment with miglustat of three patients with Niemann-Pick disease type C: follow up using brain spectroscopy. Mol Genet Metab. 2009;96:55-8 pubmed publisher
  44. Xu Z, Farver W, Kodukula S, Storch J. Regulation of sterol transport between membranes and NPC2. Biochemistry. 2008;47:11134-43 pubmed publisher
    ..Additionally, cholesterol transfer by NPC2 was found to be greatly enhanced by the unique lysosomal phospholipid lyso-bisphosphatidic acid (LBPA), suggesting an important role for LBPA in NPC2-mediated cholesterol trafficking...
  45. Park W, O Brien J, Lundquist P, Kraft D, Vockley C, Karnes P, et al. Identification of 58 novel mutations in Niemann-Pick disease type C: correlation with biochemical phenotype and importance of PTC1-like domains in NPC1. Hum Mutat. 2003;22:313-25 pubmed
    ..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...
  46. Fancello T, Dardis A, Rosano C, Tarugi P, Tappino B, Zampieri S, et al. Molecular analysis of NPC1 and NPC2 gene in 34 Niemann-Pick C Italian patients: identification and structural modeling of novel mutations. Neurogenetics. 2009;10:229-39 pubmed publisher
    ..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...
  47. Pacheco C, Kunkel R, Lieberman A. Autophagy in Niemann-Pick C disease is dependent upon Beclin-1 and responsive to lipid trafficking defects. Hum Mol Genet. 2007;16:1495-503 pubmed
  48. Walkley S, Suzuki K. Consequences of NPC1 and NPC2 loss of function in mammalian neurons. Biochim Biophys Acta. 2004;1685:48-62 pubmed
  49. Dvorakova L, Sikora J, Hrebicek M, Hulkova H, Bouckova M, Stolnaja L, et al. Subclinical course of adult visceral Niemann-Pick type C1 disease. A rare or underdiagnosed disorder?. J Inherit Metab Dis. 2006;29:591 pubmed
    ..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...
  50. Sturley S, Patterson M, Balch W, Liscum L. The pathophysiology and mechanisms of NP-C disease. Biochim Biophys Acta. 2004;1685:83-7 pubmed
  51. Wraith J, Vecchio D, Jacklin E, Abel L, Chadha Boreham H, Luzy C, et al. Miglustat in adult and juvenile patients with Niemann-Pick disease type C: long-term data from a clinical trial. Mol Genet Metab. 2010;99:351-7 pubmed publisher
    ..Overall, these data suggest that long-term miglustat therapy stabilizes neurological disease and is well tolerated in adult and juvenile patients with NP-C...
  52. Garver W, Jelinek D, Meaney F, Flynn J, Pettit K, Shepherd G, et al. The National Niemann-Pick Type C1 Disease Database: correlation of lipid profiles, mutations, and biochemical phenotypes. J Lipid Res. 2010;51:406-15 pubmed publisher
    ..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...
  53. Lebrand C, Corti M, Goodson H, Cosson P, Cavalli V, Mayran N, et al. Late endosome motility depends on lipids via the small GTPase Rab7. EMBO J. 2002;21:1289-300 pubmed
    ..We conclude that motor functions can be regulated by the membrane lipid composition via the Rab7 cycle...
  54. Ohgami N, Ko D, Thomas M, Scott M, Chang C, Chang T. Binding between the Niemann-Pick C1 protein and a photoactivatable cholesterol analog requires a functional sterol-sensing domain. Proc Natl Acad Sci U S A. 2004;101:12473-8 pubmed
    ..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...
  55. Karten B, Vance D, Campenot R, Vance J. Cholesterol accumulates in cell bodies, but is decreased in distal axons, of Niemann-Pick C1-deficient neurons. J Neurochem. 2002;83:1154-63 pubmed
    ..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...
  56. Choudhury A, Dominguez M, Puri V, Sharma D, Narita K, Wheatley C, et al. Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids and correct lipid trafficking in Niemann-Pick C cells. J Clin Invest. 2002;109:1541-50 pubmed
    ..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...
  57. Spiegel R, Raas Rothschild A, Reish O, Regev M, Meiner V, Bargal R, et al. The clinical spectrum of fetal Niemann-Pick type C. Am J Med Genet A. 2009;149A:446-50 pubmed publisher
    ..We suggest that once identified these findings, should raise the suspicion of fetal NPC. Our study further expands the antenatal clinical spectrum of NPC and provides clues to its prenatal diagnosis...
  58. Ganley I, Pfeffer S. Cholesterol accumulation sequesters Rab9 and disrupts late endosome function in NPC1-deficient cells. J Biol Chem. 2006;281:17890-9 pubmed
    ..We conclude that cholesterol contributes directly to the sequestration of Rab9 on Niemann-Pick type C cell membranes, which in turn, disrupts mannose 6-phosphate receptor trafficking...
  59. Somers K, Royals M, Carstea E, Rafi M, Wenger D, Thrall M. Mutation analysis of feline Niemann-Pick C1 disease. Mol Genet Metab. 2003;79:99-103 pubmed
    ..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...
  60. Burns M, Gaynor K, Olm V, Mercken M, LaFrancois J, Wang L, et al. Presenilin redistribution associated with aberrant cholesterol transport enhances beta-amyloid production in vivo. J Neurosci. 2003;23:5645-9 pubmed
    ..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...
  61. Vanier M, Millat G. Niemann-Pick disease type C. Clin Genet. 2003;64:269-81 pubmed
    ..These studies, conducted in various models, should ultimately lead to a better understanding of the pathophysiology of NPC and new therapeutic approaches...
  62. Verot L, Chikh K, Freydière E, Honore R, Vanier M, Millat G. Niemann-Pick C disease: functional characterization of three NPC2 mutations and clinical and molecular update on patients with NPC2. Clin Genet. 2007;71:320-30 pubmed
    ..Characterization of more naturally occurring NPC2 mutations may help to dissect further the functional domains of the protein...
  63. Linder M, Uronen R, Hölttä Vuori M, van der Sluijs P, Peranen J, Ikonen E. Rab8-dependent recycling promotes endosomal cholesterol removal in normal and sphingolipidosis cells. Mol Biol Cell. 2007;18:47-56 pubmed
    ..Our findings establish Rab8 as a key component of the regulatory machinery that leads to ABCA1-dependent removal of cholesterol from endocytic circuits...
  64. Liscum L, Sturley S. Intracellular trafficking of Niemann-Pick C proteins 1 and 2: obligate components of subcellular lipid transport. Biochim Biophys Acta. 2004;1685:22-7 pubmed
    ..We propose that the intracellular trafficking patterns of these proteins will provide clues about their function...
  65. Solomon D, Winkelman A, Zee D, Gray L, Buttner Ennever J. Niemann-Pick type C disease in two affected sisters: ocular motor recordings and brain-stem neuropathology. Ann N Y Acad Sci. 2005;1039:436-45 pubmed
    ..These neuropathologic findings correlate well with our current understanding of the anatomy and physiology of the supranuclear control of vertical gaze...
  66. Griese M, Brasch F, Aldana V, Cabrera M, Goelnitz U, Ikonen E, et al. Respiratory disease in Niemann-Pick type C2 is caused by pulmonary alveolar proteinosis. Clin Genet. 2010;77:119-30 pubmed publisher
    ..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...
  67. Pineda M, Perez Poyato M, O CALLAGHAN M, Vilaseca M, Pocovi M, Domingo R, et al. Clinical experience with miglustat therapy in pediatric patients with Niemann-Pick disease type C: a case series. Mol Genet Metab. 2010;99:358-66 pubmed publisher
    ..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...
  68. Kirkegaard T, Roth A, Petersen N, Mahalka A, Olsen O, Moilanen I, et al. Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology. Nature. 2010;463:549-53 pubmed publisher
    ..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...
  69. Macías Vidal J, Gort L, Lluch M, Pineda M, Coll M. Nonsense-mediated mRNA decay process in nine alleles of Niemann-Pick type C patients from Spain. Mol Genet Metab. 2009;97:60-4 pubmed publisher
    ..In conclusion, we confirmed that NMD process is responsible for the mRNA decay for all the analyzed NPC1 PTC-encoding mutations...
  70. Liao G, Yao Y, Liu J, Yu Z, Cheung S, Xie A, et al. Cholesterol accumulation is associated with lysosomal dysfunction and autophagic stress in Npc1 -/- mouse brain. Am J Pathol. 2007;171:962-75 pubmed
    ..These results provide strong evidence that cholesterol accumulation-induced changes in autophagy-lysosome function are closely associated with neurodegeneration in NPC...
  71. Floyd A, Yu Q, Piboolnurak P, Wraith E, Patterson M, Pullman S. Kinematic analysis of motor dysfunction in Niemann-Pick type C. Clin Neurophysiol. 2007;118:1010-8 pubmed
    ..To provide the first descriptive analysis of upper limb motor physiology in Niemann-Pick Type C disease (NP-C)...
  72. Pipalia N, Hao M, Mukherjee S, Maxfield F. Sterol, protein and lipid trafficking in Chinese hamster ovary cells with Niemann-Pick type C1 defect. Traffic. 2007;8:130-41 pubmed
    ..These data are consistent with multiple trafficking defects in both early and late endosomes in NPC cells...
  73. Chikh K, Rodriguez C, Vey S, Vanier M, Millat G. Niemann-Pick type C disease: subcellular location and functional characterization of NPC2 proteins with naturally occurring missense mutations. Hum Mutat. 2005;26:20-8 pubmed
    ..Functional characterization of the mutant proteins showed an excellent genotype-phenotype correlation in the three cases for whom a clinical history was available...
  74. Wastney M, Pentchev P, Neufeld E. Fitting a mathematical model to biological data: intracellular trafficking in Niemann-Pick C disease. Adv Exp Med Biol. 2003;537:63-75 pubmed
  75. Lange Y, Ye J, Rigney M, Steck T. Dynamics of lysosomal cholesterol in Niemann-Pick type C and normal human fibroblasts. J Lipid Res. 2002;43:198-204 pubmed
    ..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...
  76. Sugimoto Y, Ninomiya H, Ohsaki Y, Higaki K, Davies J, Ioannou Y, et al. Accumulation of cholera toxin and GM1 ganglioside in the early endosome of Niemann-Pick C1-deficient cells. Proc Natl Acad Sci U S A. 2001;98:12391-6 pubmed
    ..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...
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    ..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...
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