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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Changes of calcium binding proteins, c-Fos and COX in hippocampal formation and cerebellum of Niemann-Pick, type C mouse.
Kyunghee Byun,Daesik Kim,Enkhjaigal Bayarsaikhan,Jeehyun Oh,Jisun Kim,Grace Kwak,Goo-Bo Jeong,Seung-Mook Jo,Bonghee Lee +8 more
TL;DR: Reduction of calcium binding proteins may be one of the strong phenotypes related to the neuronal degeneration in NPC-/- mice.
Journal ArticleDOI
Human NPC1L1 and NPC1 can functionally substitute for the ncr genes to promote reproductive development in C. elegans.
Marsha Smith,Diane Levitan +1 more
TL;DR: Human NPC1L1, as well as human NPC1, can functionally substitute for the Caenorhabditis elegans genes nCr-1 and/or ncr-2, known to play a role in the process of dauer formation, a process which can be modulated by cholesterol in sensitized genetic backgrounds.
Journal ArticleDOI
Genetic background modifies phenotypic severity and longevity in a mouse model of Niemann-Pick disease type C1.
Jorge L. Rodriguez-Gil,Jorge L. Rodriguez-Gil,Jorge L. Rodriguez-Gil,Dawn E. Watkins-Chow,Laura L. Baxter,Gene Elliot,Ursula Harper,Stephen Wincovitch,Julia C. Wedel,Arturo Incao,Mylene Huebecker,Frederick J. Boehm,William S. Garver,Forbes D. Porter,Karl W. Broman,Frances M. Platt,William J. Pavan +16 more
TL;DR: This study identifies genomic regions in a new Npc1 mutant mouse model containing potential modifier variants associated with changes in phenotypic severity and lifespan.
Journal ArticleDOI
Cholesterol Pathways Affected by Small Molecules That Decrease Sterol Levels in Niemann-Pick Type C Mutant Cells
TL;DR: This approach proved successful in the identification of seven chemicals as novel inhibitors of lysosomal acid lipase (Rosenbaum et al, Biochim. 2009, 1791:1155–1165).
Journal ArticleDOI
Exploiting the Potential of Drosophila Models in Lysosomal Storage Disorders: Pathological Mechanisms and Drug Discovery.
TL;DR: In this article, the major cellular pathways implicated in LSDs pathogenesis, the approaches available for their study and the Drosophila models developed for these diseases were described and used for drug screening studies.
References
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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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