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
Current Challenges in Understanding the Cellular and Molecular Mechanisms in Niemann–Pick Disease Type C1
TL;DR: The impact of NPC1 pathology on several organ systems, as revealed in experimental animal models and humans, and an overview of current available treatment options are summarized.
Journal ArticleDOI
The AAA ATPase VPS4/SKD1 regulates endosomal cholesterol trafficking independently of ESCRT-III.
TL;DR: VPS4, an AAA ATPase that has a well‐established role in disassembling the ESCRT (endosomal sorting complex required for transport)‐III polymer, is established as an important regulator of endosomal cholesterol transport and represents the first functional separation of VPS4 from ESCRT‐III.
Journal ArticleDOI
Decreased purinergic inhibition of synaptic activity in a mouse model of Niemann-Pick disease type C.
TL;DR: It was found that the hippocampal field excitatory postsynaptic potential (fEPSP) was enhanced in NPC1 mutant mice, and adenosine release from hippocampal slices was significantly decreased in the mutant.
Journal ArticleDOI
The steroidal analog GW707 activates the SREBP pathway through disruption of intracellular cholesterol trafficking.
Jessie Zhang,Nicole Dudley-Rucker,Jan R. Crowley,Elvira Lopez-Perez,Marc Issandou,Jean E. Schaffer,Daniel S. Ory +6 more
TL;DR: Findings support a mechanism in which GW707 exerts its hypolipidemic effects through disruption of late endosomal/lysosomal sterol trafficking and subsequent stimulation of LDLr activity.
Book ChapterDOI
Miglustat Treatment May Reduce Cerebrospinal Fluid Levels of the Axonal Degeneration Marker Tau in Niemann–Pick Type C
Niklas Mattsson,Henrik Zetterberg,Simona Bianconi,Nicole M. Yanjanin,Rao Fu,Jan-Eric Månsson,Forbes D. Porter,Kaj Blennow +7 more
TL;DR: Reduced CSF T-tau levels suggests that miglustat treatment might affect axonal degeneration in Niemann-Pick disease type C, however, the results must be interpreted with caution and verified in future studies, since this pilot study was small, treatment was not randomized, and patients starting treatment had higher baseline CSFs than untreated patients.
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
Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue
TL;DR: The results are shown to favour the ferryl ion structure, or an isomer of this structure, for the higher oxidation state, and theHigher oxidation state may provisionally be named ferrylmyoglobin.
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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