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
Citations
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Journal ArticleDOI
Multidrug permeases and subcellular cholesterol transport.
TL;DR: Characterization of their protein products shows that NPC1 and ABCA1 are permeases that belong to two different superfamilies of efflux pumps, which might be important in subcellular lipid and cholesterol transport.
Journal ArticleDOI
Telomerase immortalization upregulates Rab9 expression and restores LDL cholesterol egress from Niemann-Pick C1 late endosomes.
TL;DR: The results suggest the existence of alternative endogenous therapeutic targets that can be modulated to reverse the NPC1 disease phenotype and suggest that TeRT expression leads to an increase in the transport of molecules, including cholesterol, from the E-L system, and may play a role in increasing cellular proliferation.
Journal ArticleDOI
Identification of Sites of Mannose 6-Phosphorylation on Lysosomal Proteins
TL;DR: This report describes a mass spectrometric approach to the verification of Man-6-phosphorylation based upon LC-MS of MPR-purified proteolytic glycopeptides, which provided a useful tool in validating novel MPR -purified proteins as true Man- 6-P glycoproteins and also allowed identification of low abundance components not observed in the analysis of the total Man-7-p glycoprotein mixture.
Journal ArticleDOI
Endogenous and synthetic neurosteroids in treatment of Niemann–Pick Type C disease
TL;DR: The data suggest that mouse models of neurodegeneration may be beneficial in establishing both physiologic and pharmacologic actions of neurosteroids, and further establish the wide range of functions of these compounds, which may ultimately be useful for treatment of human diseases.
Journal ArticleDOI
The Neuropsychiatry of Niemann-Pick Type C Disease in Adulthood
Mark Walterfang,Michael Fietz,Michael C Fahey,Danny Sullivan,Pamela Leane,D. Lubman,Dennis Velakoulis +6 more
TL;DR: Three young men with a variant form of Niemann-Pick type C disease, a neurodegenerative disorder related to abnormal intracellular cholesterol metabolism, who presented with psychosis in early adulthood are described.
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
Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue
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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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