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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Cholesterol metabolism in neurons and astrocytes
Frank W. Pfrieger,Nicole Ungerer +1 more
TL;DR: An understanding of cholesterol metabolism in the brain and its role in disease requires a close look at individual cell types, including neurons and astrocytes, which are identified as net producers and consumers of cholesterol.
Journal ArticleDOI
Autophagy in lysosomal storage disorders
Andrew P. Lieberman,Rosa Puertollano,Nina Raben,Susan A. Slaugenhaupt,Steven U. Walkley,Andrea Ballabio,Andrea Ballabio +6 more
TL;DR: Recent findings that have been obtained through analysis of the autophagic pathway in several types of LSDs are provided, supporting the idea that LSDs could be seen primarily as “autophagy disorders.”
Journal ArticleDOI
Characterization and immunobiology of house dust mite allergens.
TL;DR: While some estimate of the importance of allergens can be obtained from IgE binding, few analyses of T-cell responses have been made and these regulate both the development of, and the protection from sensitization.
Journal ArticleDOI
Cholesterol Oxidation Products Are Sensitive and Specific Blood-Based Biomarkers for Niemann-Pick C1 Disease
Forbes D. Porter,David E. Scherrer,Michael H. Lanier,S. Joshua Langmade,Vasumathi Molugu,Sarah E. Gale,Dana Olzeski,Rohini Sidhu,Dennis J. Dietzen,Rao Fu,Christopher A. Wassif,Nicole M. Yanjanin,Steven P. Marso,John A. House,Charles H. Vite,Jean E. Schaffer,Daniel S. Ory +16 more
TL;DR: Blood concentrations of two related oxysterols molecules were almost 10 times higher in Niemann-Pick C1 patients than in age-matched healthy controls or those with other diseases such as atherosclerosis or diabetes, suggesting that the two oxysterol molecules are accurate diagnostic markers of early clinical disease and can be used not only to monitor disease progression but also to demonstrate drug efficacy.
Journal ArticleDOI
Intracellular cholesterol transport
TL;DR: This chapter provides an overview of the recent understanding of intracellular transport of cholesterol, aimed to create a link between the well characterized biophysical properties of cholesterol in model membranes and its behavior in living cells.
References
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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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