Journal of Applied Genetics

, Volume 59, Issue 4, pp 441–447 | Cite as

Do GWAS and studies of heterozygotes for NPC1 and/or NPC2 explain why NPC disease cases are so rare?

  • Robert P. EricksonEmail author
Human Genetics • Review


Early onset Niemann-Pick C diseases are extremely rare, especially Niemann-Pick C2. Perhaps unusually for autosomal recessive diseases, heterozygotes for mutations in NPC1 manifest many biological variations. NPC2 deficiency has large effects on fertility. These features of NPC1 and NPC2 are reviewed in regard to possible negative selection for heterozygotes carrying null and hypomorphic alleles.


Niemann-Pick C disease Heterozygote disadvantage Carrier frequency Obesity Fertility Dementia 


Compliance with ethical standards

Conflict of interest

The author declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by the author.


  1. Acuna M, Gonzalez-Hodar L, Amigo L, Castro J, Morales MG, Cancino GI, Groen AK, Young J, Miquel JF, Zanlungo S (2016) Transgenic overexpression of Niemann-pick C2 protein promotes cholesterol gallstone formation in mice. J Hepatol 64:361–369CrossRefPubMedGoogle Scholar
  2. Akpovi CD, Murphy BD, Erickson RP, Pelletier R-M (2014) Dysregulation of testicular cholesterol metabolism following spontaneous mutation of the Niemann-pick C1 gene. Biol Reprod 91:1–8CrossRefGoogle Scholar
  3. Allison AC (1954) Protection afforded by sickle-cell trait against subtertian malarial infection. Br Med J 1:290–294CrossRefPubMedPubMedCentralGoogle Scholar
  4. Araki N, Ishigami T, Ushio H, Minegishi S, umemura M, Miyagi Y, Aoi I, Morinaga H, Tamura K, Toya Y, Uchino K, Umemura S (2009) Identification of NPC2 protein as interaction molecule with C2 domain of human Nedd4L. Biochem Biophys Res Commun 388:290–296CrossRefPubMedGoogle Scholar
  5. Bell CJ et al (2011) Carrier testing for severe childhood recessive diseases by next-generation sequencing. Sci Transl Med 3:65ra4CrossRefPubMedPubMedCentralGoogle Scholar
  6. Borbon I, Erickson RP (201) Interactions of NPC1 and amyloid accumulaation/deposition in the APP/PS1 mouse model of Alzheimer's. J Appl Genet 52:213–218CrossRefPubMedGoogle Scholar
  7. Boadu E, Nelson RC, Francis GA (2012) ABCA-1dependent mobilization of lysosomal cholesterol requires functional Niemann-pick C2 but not Niemann-pick C1 protein. Biochim Biophys Acta 1821:395–404Google Scholar
  8. Borbon I, Campbell E, Ke W, Erickson RP (2012) The role of decreased levels of Niemann-pick C1 intracellular cholesterol transport on obesity is reversed in the C57Bl/6J, metabolic syndrome mouse strain. J Appl Genet 53:323–330CrossRefPubMedGoogle Scholar
  9. Brown DE, Thrall MA, Walkley SU, Wurzelmann S, Wenger DA, Allison RW, Just CA (1996) Metabolic abnormalities in feline Niemann-pick type C. J Inherit Metab Dis 19:319–330CrossRefPubMedGoogle Scholar
  10. Burns M, Gaynor K, Olm V, Mercken M, LaFrancois J, Wang L, Mathews PM, Noble W, Matsuoka Y, Duff K (2003) Presenilin redistribution associated with aberrant cholesterol transport enhances beta-amyloid production in vivo. J Neurosci 23:5645–5649CrossRefPubMedGoogle Scholar
  11. Busso D, Onate-Alvarado MJ, Balboa E, Zanlungo S, Moreno RD (2009) Female infertility due to anovulation and defective steroidogenesis in NPC2 deficient mice. Mol Cell Endocrinol 315:299–307CrossRefPubMedGoogle Scholar
  12. Busso D, Onate-Alvarado MJ, Balboa E, Castro J, Lizama C, Morales G, Vargas S, Hartel S, Moreno RD, Zanlungo S (2013) Spermatozoa from mice deficient in Niemann-pick disease type C2 protein have defective cholesterol content and reduced in vitro fertilising ability. Reprod Fertil Dev 26:609–621CrossRefGoogle Scholar
  13. Cabler S, Agarwal A, Flint M, Du Plessis SS (2017) Obesity: modern man’s fertililty nemesis. Asian J Androl 12:480–489CrossRefGoogle Scholar
  14. Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N, Kuehne AI, Kranzusch PJ, Griffin AM, Ruthel G, Dal Cin P, Dye JM, Whelan SP, Chandran K, Brummelkamp TR (2011) Ebola virus entry requires the cholesterol transporter Niemann pick C1. Nature 477:340–343. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Cook DL, Gerber AN, Tapscott SJ (1998) Modelling stochastic gene expression: implications for haploinsufficiency. Proc Natl Acad Sci U S A 95:15641–15646CrossRefPubMedPubMedCentralGoogle Scholar
  16. Cross NL (2004) Reorganization of lipid rafts during capacitation of human sperm. Biol Reprod 71:1367–1373CrossRefPubMedGoogle Scholar
  17. Csepeggi G, Jiang M, Frolov A (2010) Somatic cell plasticity and Niemann-pick type C2 protein: adipocyte differentiation and function. J Biol Chem 285:30347–30354CrossRefPubMedPubMedCentralGoogle Scholar
  18. Cupidi C, Frangipane F, Gallo M, Clodomiro A, Colao R et al (2017) Role of Niemann-pick type C disease mutations in dementia. J Alzheimers Dis 55:1249–1259CrossRefPubMedGoogle Scholar
  19. Dani V, Ganot V, Priouzeau F, Furla P, Sabourault C (2014) Are Niemann-pick type C proteins key players in cnidarian–dinoflagellate endosymbioses? Mol Ecol 18:4527–4540CrossRefGoogle Scholar
  20. de Arujo LS, Vaas LA, Ribeiro-Alves M, Gefffers R, Melio AS et al (2016) Transcriptomic biomarkers for tuberculosis: evaluation of DOCK9, EPHA4 and NPC2 mRNA expression in peripheral blood. Front Microbiol 7:15686Google Scholar
  21. Donohue C, Marion S, Erickson RP (2009) Expression of Npc1 in glial cells corrects sterility in Npc1−/− mice. J Appl Genet 50:385–390CrossRefPubMedGoogle Scholar
  22. Erickson RP (2013) Current controversies in Niemann-pick C1 disease: steroids or gangliosides; neurons or neurons and glia. J Appl Genet 54:215–224CrossRefPubMedGoogle Scholar
  23. Erickson RP, Mitchison NA (2014) The low frequency of recessive disease: insights from ENU mutagenesis, severity of disease phenotype, GWAS associations, and demography: an analytical review. J Appl Genet 55:319–127CrossRefPubMedGoogle Scholar
  24. Erickson R, Kiela M, Devine P, Hoyer P, Heidenreich R (2002) Mdr1a deficiency corrects sterility in Niemann-pick C1 protein deficient female mice. Mol Reprod Dev 62:167–173CrossRefPubMedGoogle Scholar
  25. Erickson RP, Bhattacharyya A, Hunter RJ, Heidenreich RA, Cherrington NJ (2005) Liver disease with altered bile acid trans- port in Niemann–pick C mice on a high-fat, 1% cholesterol diet. Am J Physiol Gastrointest Liver Physiol 289:G300–G307CrossRefPubMedGoogle Scholar
  26. Erickson RP, Larson-Thome K, Weberg L, Szybinska A, Mossakowska M, Styczynska M, Barcikowska M, Kuznicki J (2008) Variation in NPC1, the gene encoding Niemann-pick C1, a protein involved in intracellular cholesterol transport, is associated with Alzheimer disease and/or aging in the polish population. Neurosci Lett 447:153–157CrossRefPubMedPubMedCentralGoogle Scholar
  27. Fan J, Akabane H, Graham S, Richardson L, Zhu G (2006) Sperm defects in mice lacking a functional Niemann-pick C1 protein. Mol Reprod Dev 73:1284–1291CrossRefPubMedGoogle Scholar
  28. Feng B, Tabas I (2002) ABCA1-mediated cholesterol efflux is defective in free cholesterol-loaded macrophages: mechanism involves enhanced ABCA1 degradation in a process requiring full NPC1 activity. J Biol Chem 277:43271–43280CrossRefPubMedGoogle Scholar
  29. Feng B, Yao PM, Li Y, Devlin CM, Zhang D, harding HP, Sweeney M, Rong JX, Kuriakose G, Fisher EA, Marks AR, Ron D, Tabas I (2003a) The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat Cell Biol 5:781–792CrossRefPubMedGoogle Scholar
  30. Feng B, Zhang D, Kuriakose G, Devlin CM, Kockx M, Tabas I (2003b) Niemann-pick C heterozygosity confers resistance to lesional necrosis and macrophage apoptosis in murine atherosclerosis. Proc Natl Acad Sci U S A 100:10423–10428CrossRefPubMedPubMedCentralGoogle Scholar
  31. Fiorenza MT, Dardis A, Canterini S, Erickson RP (2013) Cholesterol-metabolism-associated molecules in late onset Alzheimer’s disease. J Biol Regul Homeost Agents 27:23–36PubMedGoogle Scholar
  32. Fröhlich O, Young LG (1996) Molecular cloning and characterization of EPI-1, the major protein in chimpanzee (Pan troglodytes) cauda epididymal fluid. Biol Reprod 54:857–864CrossRefPubMedGoogle Scholar
  33. Garver WS, Hsu S-CJ, Erickson RP, Greer WL, Byers DM, Heidenreich RA (1997a) Increased expression of caveolin-1 in heterozygous Niemann-pick type 1 human fibroblasts. Biochem Biophys Res Commun 236:189–193CrossRefPubMedGoogle Scholar
  34. Garver WS, Erickson RP, Wilson JM, Colton TL, Hossain GS, Kozloski MA, Heidenreich RA (1997b) Altered expression of caveolin-1 and increased cholesterol in detergent insoluble membrane fractions from liver in mice with Niemann-pick disease type C. Biochim Biophys Acta 1361:272–280CrossRefPubMedGoogle Scholar
  35. Gevry NY, Lopes FL, Ledoux S, Murphy BD (2006) Aberrant intracellular cholesterol transport disrupts pituitary and ovarian function. Mol Endocrinol 18:1778–1788CrossRefGoogle Scholar
  36. Gwynne JT, Strauss JF 3rd (1982) The role of lipoproteins in steroidogenesis and cholesterol metabolism in steroidogenic glands. Endocr Rev 3:299–329CrossRefPubMedGoogle Scholar
  37. Hannaford J, Guo H, Chen X (2012) Involvement of cathepsins B and L in inflammation and cholesterol trafficking protein NPC2 secretion in macrophages. Obesity 21:1586–1595CrossRefGoogle Scholar
  38. Herbert AS, Davidson C, Kuehne AI, Bakken R, Braigen SZ, Gunn KE, Whelan SP, Brummelkamp TR, Twenhafel NA, Chandran K, Walkley SU, Dye JM (2015) Niemann-pick C1 is essential for Ebolavirus replication and pathogenesis in vivo. mBio 6(3):e00565–e00515. CrossRefPubMedPubMedCentralGoogle Scholar
  39. Hung YH, Walterfang M, Churilov L, Bray L, Jacobson LH, Barnham KJ, Jones NC, O’Brien TJ, Velakoulis D, Bush AL (2016) Neurological dysfunction in early maturity of a model for Niemann-pick C1 carrier status. Neurotherapeutics 13:614–622CrossRefPubMedPubMedCentralGoogle Scholar
  40. Ilnytska O, Santiana M, Hsu N-Y, Du W-L, Chen Y-H, Viktorova EG, Belov G, Brinker A, Storch J, Moore C, Dixon JL, Altan-Bonnet N (2013) Enteroviruses harness the cellular Endocytic machinery to remodel the host cell cholesterol landscape for effective viral replication. Cell Host Microbe 14:281–293CrossRefPubMedPubMedCentralGoogle Scholar
  41. Infante RE, Wang ML, Radhakrishnan A, Kwon HJ, Brown MS, Goldstein JL (2008) NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes. Proc Natl Acad Sci 105:15287–15292CrossRefPubMedGoogle Scholar
  42. Jelinek D, Heidenreich RA, Erickson RP, Garver WS (2010) Decreased Npc1 gene dosage in mice is associated with weight gain. Obesity 18:1457–1459CrossRefPubMedGoogle Scholar
  43. Jin LW, Shie FS, Maezawa I, Vincent I, Bird T (2004) 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 164:957–985CrossRefGoogle Scholar
  44. Josephs KA, Matsumoto JY, Lindor NM (2004) Heterozygous Niemann-pick disease type C presenting with tremor. Neurology 63:2189–2190CrossRefPubMedGoogle Scholar
  45. Kelly DA, Portmann B, Mowat AP, Sherlock S, Lake BD (1993) Niemann-pick disease type C: diagnosis and outcome in children, with particular reference to liver disease. J Pediatr 123:242–247CrossRefPubMedGoogle Scholar
  46. Kim H, Cun Y, Che L, Kim J, Lee S, Lee S (2017) The new obesity-associated protein, neuronal growth regulator 1 (NEGR1) is implicated in Niemann-pick disease type C(NPC2)-mediated cholesterol trafficking. Biochem Biophys Res Commun 482:1367–1374CrossRefPubMedGoogle Scholar
  47. Kirchoff C, Osterhoff C, Young L (1996) Molecular cloning and characterization of HE1, a major secretory protein of the human epididymis. Biol Reprod 54:377–387CrossRefGoogle Scholar
  48. Klein A, Amigo L, Retamal MJ, Morales MG, Miguel JF, Rigotti A, Zanlungo S (2006) NPC2 is expressed in human and murine liver and secreted into bile: potential implicaions for body cholesterol homeostasis. Hepatology 43:126–133CrossRefPubMedGoogle Scholar
  49. Kosicek M, Malnar M, Goate A, Hecimovic S (2010) Cholesterol accumulation in Niemann pick type C (NPC) model cells causes a shift in APP localization to lipid rafts. BBRC 393:404–409PubMedGoogle Scholar
  50. Kruth HS, Comly ME, Butler JD, Vanier MT, Fink JK, Wenger DA, Patel S, Pentchev PG (1986) Type C Niemann-pick disease: Abnormal metabolism of low density lipoprotein in homozygous and heterozygous fibroblasts. J Biol Chem 261:16769–16774PubMedGoogle Scholar
  51. Lamri A, Pigeyre M, Garver WS, Meyre D (2018) The extending Spectrum of NPC1-related human disorders: from Niemann-pick C1 disease to obesity. Endocr Rev 39:192–220CrossRefPubMedGoogle Scholar
  52. Larsen LB, Ravn P, Boisen A, Berglund L, Petersen TE (1997) Primary structure of EPV20, a secretory glycoprotein containing a previously uncharacterized type of domain. Eur J Biochem 243:437–441CrossRefPubMedGoogle Scholar
  53. Lek M et al (2016) Analysis of protein-coding variants in 60,706 humans. Nature 536:285–292CrossRefPubMedPubMedCentralGoogle Scholar
  54. Liu R, Zou Y, Hong J, Cao M, Cui B, Zhang H et al (2017) Rare loss-of-function variants in NPC1 predispose to human obesity. Diabetes 66:935–947CrossRefPubMedGoogle Scholar
  55. Louwette S, Regal L, Wittevrongel C, Thys C, Vandeweeghde G, Decuyper E, Leemans P, De Vos R, Van Geet C, Jaeken J, Freson K (2013) NPC1 defect results in abnormal platelet formation and function: studies in Niemann-pick disease type C1 patients and zebrafish. Hum Mol Genet 22:61–73CrossRefPubMedGoogle Scholar
  56. Malnar M, Kosicek M, Mitterreiter S, Omerbasic D, Lichtenthaler SF, Goate A, Hecimovic S (2010) Niemann-pick type C cells show cholesterol dependent decrease of APP expression at the cell surface and its increased processing through the β-secretase pathway. Biochim Biophys Acta 1802:682–691CrossRefPubMedPubMedCentralGoogle Scholar
  57. Maue RA, Burgess RW, Wang B, Wooley CM, Seburn KA, Vanier MR, Rogers MA, Chang CC, Chang T-Y, Harris BT, Graber DJ, Penatti CAA, Porter DM, Szwergold BS, Henderson LP, Totenhagen JW, Trouard TP, Borbon IA, Erickson RP (2012) A novel mouse model of Niemann-pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human mutations. Hum Mol Genet 21:730–750CrossRefPubMedGoogle Scholar
  58. Maulik M, Thinakaran G, Kar S (2013) Alteration in gene expression in mutant amyloid precursor protein transgenic mice lacking Niemann-pick C1 protein. PLoS One 8:e54605. CrossRefPubMedPubMedCentralGoogle Scholar
  59. Meyre D, Delplanque J, Chèvre JC et al (2009) Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat Genet 41:157–159CrossRefPubMedGoogle Scholar
  60. Naureckiene S, Sleat DE, Lackland H, Fensom A, Vanier MT, Wattiaux R, Jadot M, Lobel P (2000) Identification of HE1 as the second gene of Niemann-pick C disease. Science 290:2298–2301CrossRefPubMedGoogle Scholar
  61. Nunes A, Pressey SNR, Cooper JD, Soriano S (2011) Loss of amyloid precursor protein in a mouse model of Niemann-pick type C disease exacerbates its phenotype and disrupts tau homeostasis. Neurobiol Dis 42:349–359CrossRefPubMedGoogle Scholar
  62. Ong WY, Sundaram RK, Huang E, Ghoshal S, Kuman U, Pentchev PG, Patel SC (2004) Neuronal localization and association of Niemann pick C2 protein (HE1/NPC2) with the postsynaptic density. Neuroscience 128:561–570CrossRefPubMedGoogle Scholar
  63. Pacheco CD, Elrick MJ, Lieberman AP (2009) Tau deletion exacerbates the phenotype of Niemann-pick type C mice and implicates autophagy in pathogenesis. Hum Mol Genet 18:956–965CrossRefPubMedGoogle Scholar
  64. Park WD, O’Brien JF, Lundquist P, Kraf DL, Vockley CW, Karnes PS, Patterson MC, Snow K (2003) Identification of 58 novel mutations in Niemann–pick disease type C: correlation with bio-chemical phenotype and importance of PTC1–like domains in NPC1. Hum Mutat 22:313–325CrossRefPubMedGoogle Scholar
  65. Pier GB, Grout M, zaidi T, Meluleni G, Mueschenborn SS, Banting G, Ratcliff R, Evans MJ, Colledge WH (1998) Salmonella typhi uses CFTR to enter intestinal epithelial cells. Nature 393(6680):79–82CrossRefPubMedGoogle Scholar
  66. Piton A, Redin C, Mandel J-L (2013) XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing. Am J Hum Genet 93:368–383CrossRefPubMedPubMedCentralGoogle Scholar
  67. Probert F, Ruia-Rodado V, te Vruchte D, Nicoli E-R, Claridge TDS, Wassif CA, Farhat N, Porter FD, Platt FM, Grootveld M (2017) NMR analysis reveals significant differnces in the plasma metabolic profiles of Niemann pick C1 patients, heterozygous carriers, and healthy controls. Sci Report 7:6320. CrossRefGoogle Scholar
  68. Razani B, Coombs TP, Wang XB, Frank PG, Park DS, Russell RG, Li M, Tang B, Jelicks LA, Scherer PE, Lisanti MP (2002) Caveolin-1-deficient mice are lean, resistant to diet-induced obesity, and show hypertriglyceridemia with adipocyte abnormalities. J Biol Chem 277:8635–8647CrossRefPubMedGoogle Scholar
  69. Reich DE, Lander ES (2001) On the allelic spectrum of human disease. Trends Genet 17:502–510CrossRefPubMedGoogle Scholar
  70. Rodriguez-Rodriguez E, Vazques-Higuera JL, Sanchez-Juan P, Mateo I, Posueta A, Martinez-Garcia A, Frank A, Valdivieso F, Berciano J, Bullido MJ, Combarros O (2010) Epistasis between intracellular cholesterol trafficking-related genes (NPC1 and ABCA1) and Alzheimer’s disease risk. J Alzheimers Dis 21:619–625CrossRefPubMedGoogle Scholar
  71. Roff CF, Strauss JF 3rd, Goldin E, Jaffe H, Patterson MC, Agritellis GC et al (1993) The murine Niemann-pick C lesion affects testosterone production. Endocrinology 133:2913–2922CrossRefPubMedGoogle Scholar
  72. Sagiv Y, Hudspeth K, Mattner J, Schrantz N, Stern RK, Zhou D, Savage PB, Teyton L, Bendelac A (2006) Cutting edge: impaired Glycosphingolipid trafficking and NKT cell development in mice lacking Niemann-pick type C1 protein. J Immunol 177:26–30CrossRefPubMedGoogle Scholar
  73. Shi X-Z, Zhong X, Yu X-Q (2012) Drosophila melanogaster NPC2 proteins bind bacterial cell wall components and may function in immune signal pathways. Insect Biochem Mol Biol 42:545–556CrossRefPubMedPubMedCentralGoogle Scholar
  74. Speak AO, Te Vruchte D, Davis LC et al (2014) Altered distribution and function of natural killer cells in murine and human Niemann-pick disease type C1. Blood 123:51–60CrossRefPubMedPubMedCentralGoogle Scholar
  75. Subramanian K, Balch WE (2008) NPC1/NPC2 function as a tag team duo to mobilize cholesterol. Proc Natl Acad Sci U S A 105:15223–15224CrossRefPubMedPubMedCentralGoogle Scholar
  76. Sugkraroek P, Kates M, Leader A, Tanphaichitr N (1991) Levels of cholesterol and phospholipids in freshly ejaculated sperm and Percoll-gradient pelletted sperm from fertile and unexplained infertile men. Fertil Steril 55:820–827CrossRefPubMedGoogle Scholar
  77. Turner TT (1995) On the epididymis and its role in the development of the fertile ejaculate. J Androl 16:292–298PubMedGoogle Scholar
  78. Upadhyaya M, Osborn MJ, Maynard J, Kim MR, Tamanoi F, Cooper DN (1997) Mutational and functional analysis of the neurofibromatosis type 1 (NF1) gene. Hum Genet 99:88–92CrossRefPubMedGoogle Scholar
  79. Valencia J, Gomez G, Lopez W, Mesa H, Henao FJ (2017) Relationship between HSP90a, NPC2 and L-PGDS proteins to boar semen freezability. J Anim Sci Biotechnol 8:21CrossRefPubMedPubMedCentralGoogle Scholar
  80. Vanier MT (2010) Niemann–pick disease type C. Orphanet J Rare Dis 5:16CrossRefPubMedPubMedCentralGoogle Scholar
  81. Vanier MT, Miller C (2003) Niemann-pick disease type C. Clin Genet 64:269–281CrossRefPubMedGoogle Scholar
  82. Wassif CA, Cross JL, Iben J, Sanchez-Pulido I, Cougnoux A, Platta FM, Ory DS, Ponting CP, Bailey-Wilson JE, Biesecker LG, Porter FD (2016) High incidence of unrecognized visceral/neurological late-onset Niemann-pick disease type C1 predicted by analysis of massively parallel sequencing data sets. Genet Med 18:41–48CrossRefPubMedGoogle Scholar
  83. Winsor EJ, Welch JP (1978) Genetic and demographic aspects of Nova Scotia Niemann-pick disease (type D). Am J Hum Genet 30:530–538PubMedPubMedCentralGoogle Scholar
  84. Xie C, Richardson JA, Turley SD, Dietschy JM (2006) Cholesterol substrate pools and steroid hormone levels are normal in the face of mutational inactivation of NPC1 protein. J Lipid Res 47:953–963CrossRefPubMedGoogle Scholar
  85. Xue Y et al (2012) Deleterious- and disease-allele prevalence in healthy individuals: insights from current predictions, mutation databases, and population-scale resequencing. Am J Hum Genet 91:1022–1032CrossRefPubMedPubMedCentralGoogle Scholar
  86. Yamazaki T, Chang TY, Haass C, Ihara Y (2001) Accumulation and aggregation of amyloid beta-protein in late endosomes of Niemann-pick type C cells. J Biol Chem 276:4454–4460CrossRefPubMedGoogle Scholar
  87. Yang P, Sun Y-M, Liu Z-J, Tao QQ, Li H-L, Lu S-J, Wu Z-Y (2013) Association study of ABCA7 and NPC1 polymorphisms with Alzheimer’s disease in Chinese Han ethnic population. Psychiatr Genet 23:268CrossRefPubMedGoogle Scholar
  88. Yu W, Ko M, Yanagisawa K, michikawa M (2005) Neurodegeneration in heterozygous Niemann-pick type C1 (NPC1) mouse: implication of heterozygous NPC1 mutations being a risk for tauopathy. J Biol Chem 280:27296–27302CrossRefPubMedGoogle Scholar
  89. Zalata A, Hassan A, Christophe A, Comhaire F, Mostafa T (2010) Cholesterol and desmosterol in two sperm populations separated on Sil-select gradient. Int J Androl 33:528–535CrossRefPubMedGoogle Scholar
  90. Zhang M, Sun M, Dwyer NK, Comly ME, Patel SC, Sundaram R, Hanover JA, Blanchette-Mackie EJ (2003) Differential trafficking of the Niemann-pick C1 and 2 proteins highlights distinct roles in late endocytic lipic trafficking. Acta Paediatr Suppl 443:63–73Google Scholar
  91. Zhang M, Strnatka D, Donohue C, Hallows J, Vincent I, Erickson RP (2008) Astrocyte-only Npc1 reduces neuronal cholesterol and triples life span of Npc1−/− mice. J Neurosci Res 86:2848–2856CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Institute of Plant Genetics, Polish Academy of Sciences, Poznan 2018

Authors and Affiliations

  1. 1.Department of PediatricsUniversity of ArizonaTucsonUSA

Personalised recommendations