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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Genetic and pharmacological evidence implicates cathepsins in Niemann-Pick C cerebellar degeneration
TL;DR: The observation that Npc1 and Cstb deletion genetically interact to potently enhance the degenerative phenotype of the NPC cerebellum provides strong support for the notion that lysosomal membrane permeabilization contributes to cerebellar degeneration in NPC disease.
Journal ArticleDOI
Cholesterol as a factor regulating intracellular localization of annexin A6 in Niemann-Pick type C human skin fibroblasts
Malgorzata E. Sztolsztener,Agnieszka Strzelecka-Kiliszek,Slawomir Pikula,Anna Tylki-Szymańska,Joanna Bandorowicz-Pikula +4 more
TL;DR: It is found that in NPC cells AnxA6 translocates to the perinuclear region containing late endosomes (LE) loaded with cholesterol and therefore may contribute to the pathology of the NPC disease.
Journal ArticleDOI
Sphingolipid signalling mediates mitochondrial dysfunctions and reduced chronological lifespan in the yeast model of Niemann‐Pick type C1
Rita Vilaça,Rita Vilaça,Elísio Silva,Elísio Silva,André Nadais,André Nadais,Vitor Hugo Teixeira,Vitor Hugo Teixeira,Nabil Matmati,Joana Gaifem,Yusuf A. Hannun,Maria Clara Sá Miranda,Vítor Costa,Vítor Costa +13 more
TL;DR: It is suggested that sphingolipid signalling through Pkh1p‐Sch9p mediate mitochondrial dysfunction, oxidative stress sensitivity and shortened chronological lifespan in the yeast model of Niemann‐Pick type C disease.
Journal ArticleDOI
Intracellular Cholesterol and Phospholipid Trafficking: Comparable Mechanisms in Macrophages and Neuronal Cells
Gerd Schmitz,Evelyn Orsó +1 more
TL;DR: The present study focuses on the major protein players that establish cellular distribution of cholesterol and phospholipids, and examples are presented that trafficking dysfunctions lead to disease development, or contribute to the pathogenesis of diseases such as Alzheimer disease and atherosclerosis.
Journal ArticleDOI
Pharmacological Sequestration of Intracellular Cholesterol in Late Endosomes Disrupts Ruffled Border Formation in Osteoclasts
Haibo Zhao,H. Kalervo Väänänen +1 more
TL;DR: Cholesterol homeostasis regulates late endosomal/lysosomal trafficking and polarized secretion in resorbing osteoclasts, and shows that the ruffled border lacks a lateendosomal lipid, LBPA, but is enriched in cholesterol.
References
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Book
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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.
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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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