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
Reads0
Chats0
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
More filters
Journal ArticleDOI
Lipoprotein receptors and cholesterol in APP trafficking and proteolytic processing, implications for Alzheimer's disease.
Maria Paz Marzolo,Guojun Bu +1 more
TL;DR: The current understanding of the roles of lipoprotein receptors and cholesterol in APP trafficking and processing and their implication for AD pathogenesis and therapy is summarized.
Journal ArticleDOI
Defective cholesterol trafficking in Niemann-Pick C-deficient cells.
Kyle B. Peake,Jean E. Vance +1 more
TL;DR: Data supporting a model in which movement of cholesterol out of LE/L is mediated by the sequential action of the two NPC proteins is reviewed, including evidence that treatment of NPC‐deficient mice with the cholesterol‐binding compound, cyclodextrin, markedly attenuates neurodegeneration, and increases life‐span, of NPC1‐ deficient mice.
Journal ArticleDOI
Cellular pathology of Niemann-Pick type C disease
Elina Ikonen,Maarit Hölttä-Vuori +1 more
TL;DR: The importance of NPC as a model for subcellular lipid imbalance in studying more common diseases, such as Alzheimer's and cardiovascular diseases, is discussed and the contribution of other lipids in the cellular pathogenesis is addressed.
Journal ArticleDOI
Continuous transport of a small fraction of plasma membrane cholesterol to endoplasmic reticulum regulates total cellular cholesterol.
TL;DR: This work establishes the cholesterol-binding domain 4 of anthrolysin O (ALOD4) as a reversible inhibitor of cholesterol transport from PM to endoplasmic reticulum (ER) and demonstrates that continuous PM-to-ER cholesterol transport allows ER to constantly monitor PM cholesterol levels, and respond rapidly to small declines in cellular cholesterol by activating SREBPs, increasing cholesterol uptake and synthesis.
Journal ArticleDOI
Life in the lumen: The multivesicular endosome.
TL;DR: This review will allude to the size limitations imposed on intralumenal vesicle functions and speculate on the possible role of LBPA as calcium chelator in the acidic calcium stores of endo‐lysosomes.
References
More filters
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.
Related Papers (5)
Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis.
Eugene D. Carstea,Jill A. Morris,Katherine G. Coleman,Stacie K. Loftus,Dana Zhang,Christiano Cummings,Jessie Z. Gu,Melissa A. Rosenfeld,William J. Pavan,David B. Krizman,James W. Nagle,M H Polymeropoulos,Stephen L. Sturley,Yiannis A. Ioannou,Maureen E. Higgins,Marcella E. Comly,Adele Cooney,Anthony Brown,Christine R. Kaneski,E. Joan Blanchette-Mackie,Nancy K. Dwyer,Edward B. Neufeld,Ta-Yuan Chang,Laura Liscum,Jerome F. Strauss,Kousaku Ohno,Marsha Zeigler,Rivka Carmi,J Sokol,David Markie,Raymond R. O'Neill,O. P. van Diggelen,Milan Elleder,Marc C. Patterson,Roscoe O. Brady,Marie T. Vanier,Peter G. Pentchev,Danilo A. Tagle +37 more