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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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Journal ArticleDOI

Accumulation of sphingomyelin in Niemann-Pick disease type C cells disrupts Rab9-dependent vesicular trafficking of cholesterol

TL;DR: Results indicate that SM negatively regulates the Rab 9‐dependent vesicular trafficking of cholesterol, and a reduction in SM levels in NPC cells recovers the Rab9‐dependentVesicular Trafficking defect.
Journal ArticleDOI

Multiple-mutation at a potential ligand-binding region decreased allergenicity of a mite allergen Der f 2 without disrupting global structure

TL;DR: Results indicate that the effect of multiple‐mutations within one IgE‐binding area on allergenicity of Der f 2, P34/95/99A, is effective when designing allerGEN‐vaccines, which achieve less allergenicicity for a broad population of patients without disrupting the global structure.
Journal ArticleDOI

Sphingolipids and mitochondrial function in budding yeast

TL;DR: A pivotal signaling role for SLs in maintaining correct mitochondrial function in budding yeast is suggested, and the retrograde response, a signaling event originating from mitochondria to the nucleus, which results in the induction of nuclear target genes is described.
Book ChapterDOI

Preliminary Results on Long-Term Potentiation-Like Cortical Plasticity and Cholinergic Dysfunction After Miglustat Treatment in Niemann-Pick Disease Type C.

TL;DR: Assessment of multiple neurological, neuropsychological and neurophysiological biomarkers using a transcranial magnetic stimulation multi-paradigm approach in two patients with NPC could help to confirm the diagnosis of NPC, and may give an indication of prognostic outcomes in pharmacological trials.
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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