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
Metazoan and microbial models of Niemann–Pick Type C disease
TL;DR: It is described how conservation of sequences and their biological roles in a variety of microbial and metazoan model systems may act as roadmaps to understanding this syndrome in humans.
Journal ArticleDOI
Spermatozoa from mice deficient in Niemann-Pick disease type C2 (NPC2) protein have defective cholesterol content and reduced in vitro fertilising ability.
Dolores Busso,María José Oñate-Alvarado,Elisa Balboa,Juan Castro,Carlos Lizama,Gabriela Morales,Susana Vargas,Steffen Härtel,Ricardo D. Moreno,Silvana Zanlungo +9 more
TL;DR: The ability of spermatozoa to undergo events influenced by epididymal maturation, such as capacitation and fertilisation, were compared between WT and NPC2(-/-) mice, suggesting that NPC2 could be involved in regulating cholesterol levels in spermatozosa during epididcyalmaturation.
Journal ArticleDOI
Genetic dissection of a cell-autonomous neurodegenerative disorder: lessons learned from mouse models of Niemann-Pick disease type C.
Manuel E. Lopez,Matthew P. Scott +1 more
TL;DR: Progress in mouse-model-based studies of NPC disease is reviewed, specifically focusing on the subtype that is caused by a deficiency in NPC1, a sterol-binding late endosomal membrane protein involved in lipid trafficking.
Journal ArticleDOI
Niemann-Pick type C disease associated with peripheral neuropathy.
Dimitrios I. Zafeiriou,Panagiota Triantafyllou,N. Gombakis,Euthymia Vargiami,Chaido Tsantali,Eleni M. Michelakaki +5 more
TL;DR: A 3 1/2-year-old patient with Niemann-Pick type C disease, who presented with regression in both cognitive and motor domains, is described, and bone marrow examination revealed foam cells, and cholesterol esterification studies found massive accumulation of unesterified cholesterol and very low intracellular esterified cholesterol.
Journal ArticleDOI
Concurrent increase of cholesterol, sphingomyelin and glucosylceramide in the spleen from non‐neurologic Niemann–Pick type C patients but also patients possibly affected with other lipid trafficking disorders
TL;DR: The spleen lipid findings with a concurrent accumulation of cholesterol, sphingomyelin and glucosylceramide (Acc‐CSG) allowed us to suggest NPC diagnoses for patients, who were free of neurologic symptoms and may be a candidate for a different lipid trafficking disorder.
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.
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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