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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Autophagy in the physiology and pathology of the central nervous system.
Vassiliki Nikoletopoulou,M-E Papandreou,M-E Papandreou,Nektarios Tavernarakis,Nektarios Tavernarakis +4 more
TL;DR: Emerging evidence is presented indicating that constitutive autophagic fluxin neurons has essential roles in key neuronal processes under physiological conditions, and how perturbations of the autophile pathway may underlie diverse pathological phenotypes in neurons associated with neurodevelopmental and neurodegenerative diseases are discussed.
Journal ArticleDOI
Niemann-Pick Type C Disease and Intracellular Cholesterol Trafficking
Ta-Yuan Chang,Patrick C. Reid,Shigeki Sugii,Nobutaka Ohgami,Jonathan C. Cruz,Catherine C.Y. Chang +5 more
TL;DR: This work presents a novel and scalable approach to gene expression engineering that allows for real-time measurement of the activity of T. Y. Chang’s Tournaisian factor, which is important for understanding the immune response to infectious disease.
Journal ArticleDOI
Cyclodextrin overcomes the transport defect in nearly every organ of NPC1 mice leading to excretion of sequestered cholesterol as bile acid
Benny Liu,Charina M. Ramirez,Anna M. Miller,Joyce J. Repa,Stephen D. Turley,John M. Dietschy +5 more
TL;DR: It is demonstrated that CYCLO administration acutely reverses the cholesterol transport defect seen in the NPC1 mouse at any age, and this reversal allows the sequestered sterol to be excreted from the body as bile acid.
Journal ArticleDOI
The pathophysiology and mechanisms of NP-C disease.
TL;DR: The molecular isolation of NPC1 and NPC2, the genes defective in patients with Niemann-Pick disease type C (NP-C) has heralded in an exponential increase in our understanding of this syndrome and thus of human intracellular sterol transport as mentioned in this paper.
Journal ArticleDOI
Inactivation of liver X receptor β leads to adult-onset motor neuron degeneration in male mice
TL;DR: Male mice with inactivated liver X receptor (LXR) beta suffer from adult-onset motor neuron degeneration and it is speculated that absence of LXRbeta leads to pathological accumulation of sterols and lipids that may themselves be neurotoxic or may modulate intracellular pathways and thereby predispose motor neurons to degeneration.
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
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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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