Complex lipid trafficking in Niemann‐Pick disease type C

Marie T. Vanier1
1Institut National de la Santé et de la Recherche Médicale U820 Université Lyon‐1 EA4611, Faculté de Médecine Lyon‐Est 7 Rue G. Paradin Lyon 69008 France

Tóm tắt

Abstract

Niemann‐Pick disease type C (NPC) is an atypical lysosomal storage disease resulting from mutations in one of two genes, either NPC1 or NPC2. Although a neurovisceral disorder, it is above all a neurodegenerative disease in the vast majority of patients. Not an enzyme deficiency, it is currently conceived as a lipid trafficking disorder. Impaired egress of cholesterol from the late endosomal/lysosomal (LE/L) compartment is a specific and key element of the pathogenesis, but other lipids, more specially sphingolipids, are also involved, and there are indications for further abnormalities. The full function of the NPC1 and NPC2 proteins is still unclear. This review provides a reappraisal of lipid storage and lysosomal enzymes activities in tissues/cells from NPC patients and animal models. It summarizes the current knowledge on the NPC1 and NPC2 proteins and their function in transport of cholesterol within the late endosomal‐lysosomal compartment, with emphasis on differences between systemic organs and the brain; it also discusses regulation by membrane lipids of the NPC2‐mediated cholesterol trafficking, interplay between cholesterol and sphingomyelin, the metabolic origin of glycosphingolipids stored in brain, and the putative role of free sphingoid bases in pathogenesis. Brief mention is finally made of diseases affecting other genes that were very recently shown to impact the “NPC pathway”.

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Tài liệu tham khảo

Amraoui Y, 2014, Oxysterols in Niemann‐Pick type C: limitations of sensitivity and specificity, J Inherit Metab Dis, 37, S150

10.1523/JNEUROSCI.1317-11.2011

10.1186/1750-1172-8-34

10.1194/jlr.P048603

10.1111/j.1600-0854.2012.01379.x

10.1016/j.cca.2014.07.010

10.1126/science.277.5323.228

10.1074/jbc.M801463200

10.1091/mbc.e04-05-0432

10.1371/journal.pone.0006951

10.1073/pnas.1110439108

10.1111/j.1600-0854.2010.01046.x

10.4161/auto.22501

10.1194/jlr.M040618

10.1111/j.1471-4159.2010.07014.x

10.1074/jbc.M708735200

10.1016/0005-2760(92)90236-O

10.1074/jbc.M109.037622

10.1006/mgme.1999.2882

10.1194/jlr.D050278

10.1046/j.1471-4159.2002.01220.x

10.1194/jlr.M029942

10.1074/jbc.M114.559914

10.1016/j.febslet.2009.10.021

10.1016/S0021-9258(18)66632-3

10.1016/j.cell.2009.03.049

10.1111/j.1471-4159.2010.07034.x

10.1194/jlr.M800180-JLR200

10.4161/auto.19469

10.1194/jlr.D044024

10.1093/hmg/9.7.1087

10.1038/nm.1876

10.1523/JNEUROSCI.5981-10.2011

10.1016/j.stemcr.2014.03.014

10.1093/hmg/ddr505

10.1016/0006-291X(81)91496-0

10.1038/emboj.2012.53

10.1126/science.290.5500.2298

Patterson MC, 2001, The Metabolic and Molecular Bases of Inherited Disease, 3611

10.1016/j.ymgme.2012.03.012

10.1186/1750-1172-8-12

10.1016/0005-2760(80)90116-2

10.1096/fasebj.1.1.3609608

10.1001/archneur.1969.00480090015001

10.1146/annurev-genom-091212-153412

10.1111/tra.12046

10.1126/scitranslmed.3001417

10.1038/14084

10.1074/jbc.M005296200

10.1194/jlr.D300032-JLR200

10.1007/s004390100531

10.1023/A:1022501702403

10.1016/0925-4439(94)90021-3

10.1042/bj3250787

10.1159/000112179

10.1074/jbc.M313517200

10.1016/j.celrep.2013.10.042

10.4161/auto.28623

10.1073/pnas.0308456101

10.1002/pmic.201200205

Spence MW, 1989, The metabolic and molecular bases of inherited disease, 1655

10.1097/NEN.0b013e31825414a6

10.1016/j.bbalip.2009.02.001

10.1016/j.ymgme.2005.07.025

10.1007/BF01800716

10.1111/j.1471-4159.1973.tb06031.x

10.1194/jlr.M037325

10.1242/dmm.010124

10.1194/jlr.R047837

10.1016/0005-2760(83)90218-7

10.1023/A:1022575511354

10.1186/1750-1172-5-16

VanierMT LatourP(2015)Laboratory diagnosis of Niemann‐Pick type C: the filipin staining test.Meth Cell Biol in press

10.1034/j.1399-0004.2003.00147.x

10.1002/9781118514672.ch11

10.1111/j.1750-3639.1998.tb00143.x

10.1016/0009-8981(80)90309-5

10.1111/j.1399-0004.1988.tb03460.x

10.1007/BF01797928

10.1016/0925-4439(91)90069-L

Vanier MT, 1996, Genetic heterogeneity in Niemann‐Pick C disease: a study using somatic cell hybridization and linkage analysis, Am J Hum Genet, 58, 118

10.1016/j.ymgme.2010.11.148

10.1016/j.bbalip.2004.08.011

10.1016/j.bbamcr.2008.11.014

10.1042/BC20070171

10.1016/j.cmet.2010.05.016

10.1111/j.1471-4159.1985.tb04044.x

10.1194/jlr.M500131-JLR200

10.1038/ng.2325

10.1007/s10545-013-9626-y

10.1073/pnas.1112751108

10.1371/journal.pgen.1003462

10.1093/hmg/ddr372

10.1093/jnen/60.1.49

10.1111/j.1651-2227.2003.tb00224.x

10.1186/1750-1172-9-82

10.1016/j.ajpath.2011.04.017