Journal ArticleDOI
Identification of HE1 as the Second Gene of Niemann-Pick C Disease
Saule Naureckiene,David E. Sleat,David E. Sleat,Henry Lackland,Anthony H. Fensom,Marie T. Vanier,Robert Wattiaux,Michel Jadot,Peter Lobel,Peter Lobel +9 more
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TLDR
Treatment of NP-C2 fibroblasts with exogenous recombinant HE1 protein ameliorated lysosomal accumulation of low density lipoprotein-derived cholesterol.Abstract:
Niemann-Pick type C2 disease (NP-C2) is a fatal hereditary disorder of unknown etiology characterized by defective egress of cholesterol from lysosomes. Here we show that the disease is caused by a deficiency in HE1, a ubiquitously expressed lysosomal protein identified previously as a cholesterol-binding protein. HE1 was undetectable in fibroblasts from NP-C2 patients but present in fibroblasts from unaffected controls and NP-C1 patients. Mutations in the HE1 gene, which maps to chromosome 14q24.3, 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.read more
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Misassembled mutant CFTR in the distal secretory pathway alters cellular lipid trafficking
Journal ArticleDOI
Systemic AAV9 gene therapy improves the lifespan of mice with Niemann-Pick disease, type C1.
Randy J. Chandler,Ian M. Williams,Alana L. Gibson,Cristin Davidson,Arturo Incao,Brandon T. Hubbard,Forbes D. Porter,William J. Pavan,Charles P. Venditti +8 more
TL;DR: The results provide the first demonstration that gene therapy may represent a therapeutic option for NPC1 patients and suggest that extraneuronal NPC1 expression can further augment the lifespan of the Npc1-/- mice after systemic AAV gene delivery.
Journal ArticleDOI
Lysosomal and Mitochondrial Liaisons in Niemann-Pick Disease.
Sandra Torres,Elisa Balboa,Silvana Zanlungo,Carlos Enrich,Carmen García-Ruiz,José C. Fernández-Checa +5 more
TL;DR: A better understanding of the lysosomal and mitochondrial interactions and trafficking may identify novel targets for the treatment of Niemann-Pick disease.
Journal ArticleDOI
Mechanisms of nonvesicular lipid transport.
TL;DR: The role of non-vesicular lipid transport has been discussed in this article, where a review describes what we know about non-veto lipid transfer mechanisms while also identifying many remaining unknowns: How do LTPs facilitate lipid movement from and into membranes, do LTLTPs require accessory proteins for efficient transfer in vivo, and how is directionality of transport determined?
Journal ArticleDOI
Accounting for protein subcellular localization: A compartmental map of the rat liver proteome
Michel Jadot,Marielle Boonen,Jacqueline Thirion,Nan Wang,Jinchuan Xing,Caifeng Zhao,Abla Tannous,Meiqian Qian,Haiyan Zheng,John K. Everett,Dirk F. Moore,David E. Sleat,Peter Lobel +12 more
TL;DR: Accounting for total intracellular distribution improves quality of organelle assignments and assigns proteins with multiple locations, and provides quantitative data and error estimates describing the distribution of each protein among the eight major cellular compartments.
References
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Book
The Metabolic and Molecular Bases of Inherited Disease
TL;DR: In this paper, the authors present a list of disorders of MITOCHONDRIAL FUNCTION, including the following: DISORDERS OF MIOCHONDRIC FERTILITY XIX, XVI, XIX.
Journal ArticleDOI
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Journal ArticleDOI
Association of Mutations in a Lysosomal Protein with Classical Late-Infantile Neuronal Ceroid Lipofuscinosis
David E. Sleat,Robert J. Donnelly,Henry Lackland,Henry Lackland,Chang Gong Liu,Istvan Sohar,Istvan Sohar,Raju K. Pullarkat,Peter Lobel,Peter Lobel +9 more
TL;DR: In this paper, the mannose 6-phosphate modification of newly synthesized lysosomal enzymes was used as an affinity marker, and a single protein was identified that is absent in LINCL.
Journal ArticleDOI
Niemann–Pick C1 Is a Late Endosome-Resident Protein That Transiently Associates with Lysosomes and the Trans-Golgi Network
TL;DR: Characterizing the subcellular location of the NPC1 protein suggests that U18666A may inhibit the retrograde transport of NPC1 from lysosomes to late endosomes for subsequent transfer to the trans-Golgi network.
Journal Article
Genetic heterogeneity in Niemann-Pick C disease: a study using somatic cell hybridization and linkage analysis.
TL;DR: In this article, the authors conducted a study on skin fibroblast cultures from 32 unrelated Niemann-Pick C patients covering the range of known clinical and biochemical phenotypes.
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