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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Lipid-mediated motor-adaptor sequestration impairs axonal lysosome delivery leading to autophagic stress and dystrophy in Niemann-Pick type C
Joseph C. Roney,Sunan Li,Tamar Farfel-Becker,Ning Huang,Tao Sun,Yuxiang Xie,Xiu-Tang Cheng,Mei-Yao Lin,Frances M. Platt,Zu-Hang Sheng +9 more
TL;DR: In this paper, the authors demonstrate a pathological mechanism by which altered membrane lipid composition impairs lysosome delivery into axons and provide biological insights into the translational application of 2-hydroxypropyl-β-cyclodextrin (HPCD) in restoring axonal homeostasis at early stages of Niemann-Pick disease.
Journal ArticleDOI
Changes to cholesterol trafficking in macrophages by Leishmania parasites infection
Geo Semini,Daniel Paape,Athina Paterou,Juliane Schroeder,Martin E. Barrios-Llerena,Toni Aebischer,Toni Aebischer +6 more
TL;DR: In this paper, the authors found that after infection by leishmaniases, cholesterol sequestration happened early after infection and was functionally significant as it correlated with the upregulation of mRNA-encoding proteins required for cholesterol biosynthesis.
Journal ArticleDOI
Pulmonary abnormalities in animal models due to Niemann-Pick type C1 (NPC1) or C2 (NPC2) disease.
Blair R. Roszell,Jian-Qin Tao,Kevin Yu,Ling Gao,Shaohui Huang,Yue Ning,Sheldon I. Feinstein,Charles H. Vite,Sandra R. Bates +8 more
TL;DR: With the exception of lamellar body size, the lung phenotype seen in the NPC1 and NPC2 mutant mice were similar, and the lack of NPC1 or NPC2 proteins resulted in a disruption of the type II cell surfactant system contributing to pulmonary abnormalities.
Journal ArticleDOI
Differences in Niemann-Pick disease Type C symptomatology observed in patients of different ages.
Eugen Mengel,Mercedes Pineda,Christian J. Hendriksz,Mark Walterfang,Juan V. Torres,Stefan A. Kolb +5 more
TL;DR: These analyses provide a comprehensive overview of symptomatology observed in a large combined cohort of patients with NP-C and controls across a wide range of ages, taking into account age-specific manifestations and their possible correlations.
Journal ArticleDOI
Phenotypic heterogeneity of Niemann-Pick disease type C in monozygotic twins.
Alberto Benussi,Antonella Alberici,Enrico Premi,Valeria Bertasi,Maria Cotelli,Marinella Turla,Andrea Dardis,Stefania Zampieri,Eleonora Marchina,Barbara Paghera,Francesca Gallivanone,Isabella Castiglioni,Alessandro Padovani,Barbara Borroni +13 more
TL;DR: This case supports the phenotypic variability of Mendelian inherited disorders in monozygotic twins, likely due to epigenetic differences and post-zygotic mutagenesis.
References
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Book
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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
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Journal Article
Genetic heterogeneity in Niemann-Pick C disease: a study using somatic cell hybridization and linkage analysis.
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