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Journal ArticleDOI

Identification of HE1 as the Second Gene of Niemann-Pick C Disease

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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.

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Cloning and characterization of a shrimp ML superfamily protein

TL;DR: The cDNA and gene of an ML protein from an important white shrimp Litopenaeus vannamei is identified and it is suggested that the LvML may play roles in the shrimp innate immunity.
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The role of lipids in atherogenesis

TL;DR: The role of oxysterols, triglycerides, fatty acids, and phospholips in atherogenesis are also described and modified of the lipid droplets fluidity by lipid composition is an important factor in susceptibility to this cholesterol efflux.
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Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: a prospective observational study

TL;DR: The utility of plasma chitotriosidase (ChT) and Chemokine (C–C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine(PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP- C is assessed.
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Somatic Cell Plasticity and Niemann-Pick Type C2 Protein FIBROBLAST ACTIVATION

TL;DR: It is shown that NPC2 deficiency in human fibroblasts confers their activation, and a novel mechanism where NPC2 by negatively regulating ERK 1/2 MAPK phosphorylation may efficiently suppress development of maladaptive tissue remodeling and inflammation is highlighted.
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Computational analysis of human disease-associated genes and their protein products

TL;DR: Comparative genomics and sequence analysis are enabling us to identify counterparts of many human disease genes in model organisms, which should accelerate the pace of research and drug development to combat human diseases.
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

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

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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