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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A human neuronal model of Niemann Pick C disease developed from stem cells isolated from patient’s skin
Natascha Bergamin,Andrea Dardis,Antonio Paolo Beltrami,Daniela Cesselli,Silvia Rigo,Stefania Zampieri,Rossana Domenis,Bruno Bembi,Carlo Alberto Beltrami +8 more
TL;DR: A human neuronal model of NPC disease is generated through the induction of differentiation of stem cells obtained from patient’s easily accessible sources and may be applied to easily generate human neuronal models of other neurodegenerative diseases.
Journal ArticleDOI
Heterogeneity and frequency of movement disorders in juvenile and adult-onset Niemann-Pick C disease
Mathieu Anheim,Ouhaid Lagha-Boukbiza,Marie-Céline Fleury-Lesaunier,Maria-Paola Valenti-Hirsch,Edouard Hirsch,Hélène Gervais-Bernard,Emmanuel Broussolle,Emmanuel Broussolle,Stéphane Thobois,Stéphane Thobois,Marie T. Vanier,Philippe Latour,Christine Tranchant +12 more
TL;DR: Treatment with miglustat should be considered in case of unexplained movement disorders, even when VSGP or cataplexy are not reported, and Filipin staining remains a strong support for the diagnosis.
Journal ArticleDOI
Guilty until proven innocent: the case of NPC1 and cholesterol.
TL;DR: A new hypothesis for the potential action or function of the NPC1 protein in the endosome is proposed and the relationship of NPC2 and NPC1 is also discussed.
Journal ArticleDOI
Niemann–Pick type C disease: Novel NPC1 mutations and characterization of the concomitant acid sphingomyelinase deficiency
Hiroaki Tamura,Tsutomu Takahashi,Nobuhiro Ban,Hiroyuki Torisu,Haruaki Ninomiya,Goro Takada,Nobuya Inagaki +6 more
TL;DR: Study of NPC fibroblasts demonstrated that the subcellular localization of ASM was preserved, suggesting that the high content of lysosomal cholesterol was not responsible for the decreased ASM activity.
Journal ArticleDOI
Hydroxypropyl-beta and -gamma cyclodextrins rescue cholesterol accumulation in Niemann–Pick C1 mutant cell via lysosome-associated membrane protein 1
TL;DR: It is proposed that HPβCD and HPγCD facilitate cholesterol export from the LE/LY compartments via the LAMP-1 protein, which may play a crucial role in cholesterol trafficking at the LE/(LY) compartments when there is no functional NPC1 protein.
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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