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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Niemann-Pick C disease in Spain: clinical spectrum and development of a disability scale.
TL;DR: In this series, splenomegaly is present in 96% of patients, even in late onset forms during the first years of life, and a disability scale could be useful for monitoring evolution, establishing possible phenotypic correlations and evaluating future therapies.
Journal ArticleDOI
Drosophila melanogaster as a Model Organism of Brain Diseases
Astrid Jeibmann,Werner Paulus +1 more
TL;DR: This review considers what has been gleaned from invertebrate models of neurodegenerative diseases, including Alzheimer's disease, Parkinson’s disease, metabolic diseases such as Leigh disease, Niemann-Pick disease and ceroid lipofuscinoses, tumor syndromes such as neurofibromatosis and tuberous sclerosis, epilepsy as well as CNS injury.
Journal ArticleDOI
Cholesterol Accumulation Sequesters Rab9 and Disrupts Late Endosome Function in NPC1-deficient Cells
Ian G. Ganley,Suzanne R. Pfeffer +1 more
TL;DR: It is concluded that cholesterol contributes directly to the sequestration of Rab9 on Niemann-Pick type C cell membranes, which in turn, disrupts mannose 6-phosphate receptor trafficking.
Journal ArticleDOI
Niemann-Pick disease type C symptomatology: an expert-based clinical description.
Eugen Mengel,Hans-Hermann Klünemann,Charles Marques Lourenço,Christian J. Hendriksz,Frédéric Sedel,Mark Walterfang,Stefan A. Kolb +6 more
TL;DR: A detailed and descriptive picture of NP-C signs and symptoms may help improve disease detection and early diagnosis, so that therapy with miglustat (Zavesca®), the only available treatment approved to date, can be started as soon as neurological symptoms appear, in order to slow disease progression.
Journal ArticleDOI
Conditional Niemann-Pick C mice demonstrate cell autonomous Purkinje cell neurodegeneration
Matthew J. Elrick,Christopher D. Pacheco,Ting Yu,Nahid Dadgar,Vikram G. Shakkottai,Christopher Ware,Henry L. Paulson,Andrew P. Lieberman +7 more
TL;DR: It is established that Npc1 deficiency leads to cell autonomous, selective neurodegeneration and suggest that the ataxic symptoms of NPC disease arise from Purkinje cell death rather than cellular dysfunction.
References
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Book
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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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