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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NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes
Rodney E. Infante,Michael L. Wang,Arun Radhakrishnan,Hyock Joo Kwon,Michael S. Brown,Joseph L. Goldstein +5 more
TL;DR: An in vitro assay is established to measure transfer of [3H]cholesterol between these two proteins and phosphatidylcholine liposomes, finding that NPC2 may be essential to deliver or remove cholesterol from NPC1, an interaction that links both proteins to the cholesterol egress process from lysosomes.
Journal ArticleDOI
Early steps in steroidogenesis: intracellular cholesterol trafficking: Thematic Review Series: Genetics of Human Lipid Diseases
TL;DR: Early steps in steroid biosynthesis are addressed, including how cholesterol transport to the cholesterol-poor outer mitochondrial membrane (OMM) appears to involve cholesterol transport proteins, and how chronic steroidogenic capacity is determined by CYP11A1 gene transcription.
Journal ArticleDOI
PRINCIPLES OF LYSOSOMAL MEMBRANE DIGESTION: Stimulation of Sphingolipid Degradation by Sphingolipid Activator Proteins and Anionic Lysosomal Lipids
Thomas Kolter,Konrad Sandhoff +1 more
TL;DR: Glycosphingolipid activator proteins not only facilitate glycolipid digestion but also act as glycolIPid transfer proteins facilitating the association of lipid antigens with immunoreceptors of the CD1 family.
Journal ArticleDOI
Cholesterol metabolism and homeostasis in the brain.
Juan Zhang,Qiang Liu +1 more
TL;DR: This review will seek to integrate current knowledge about the brain cholesterol metabolism with molecular mechanisms and show how cholesterol metabolism and its complex homeostasis regulation are currently poorly understood.
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Chronic Cyclodextrin Treatment of Murine Niemann-Pick C Disease Ameliorates Neuronal Cholesterol and Glycosphingolipid Storage and Disease Progression
Cristin Davidson,Nafeeza Ali,Matthew C. Micsenyi,Gloria Stephney,Sophie Renault,Kostantin Dobrenis,Daniel S. Ory,Marie T. Vanier,Steven U. Walkley +8 more
TL;DR: Treating Niemann-Pick type C mice with CD delayed clinical disease onset, reduced intraneuronal storage and secondary markers of neurodegeneration, and significantly increased lifespan of both Npc1−/− and Npc2+/− mice.
References
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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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