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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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Citations
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Stimulation of mGluR1/5 Improves Defective Internalization of AMPA Receptors in NPC1 Mutant Mouse.

TL;DR: The data imply that abnormal internalization of AMPA receptors is a critical mechanism for neuronal dysfunction and the correction of dysfunctional mGluR1/5 is a potential therapeutic strategy for NPC1 disease.
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Niemann-Pick C2 Protein Expression Regulates Lithogenic Diet-Induced Gallstone Formation and Dietary Cholesterol Metabolism in Mice

TL;DR: This work indicates that hepatic NPC2 expression is an important factor in the regulation of diet-derived cholesterol metabolism and disposal as well as in diet-induced cholesterol gallstone formation in mice.

The Neuropsychiatry of Hyperkinetic Movement Disorders: Insights from Neuroimaging into the Neural Circuit Bases of Dysfunction

TL;DR: It is argued that neuropsychiatric symptoms are integral to a thorough phenomenological account of hyperkinetic movement disorders, and that these disorders can be conceptualized as disorders of complex subcortical networks with distinct functional architectures.

Regulation of vitamin E and the tocopherol transfer protein

TL;DR: The data suggests that TTP-expressing astrocytes distribute tocopherol to protect neurons from oxidative-stress induced damage, which is similar for other lipids, includingructose.
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Two-dimensional complementary deoxyribonucleic acid electrophoresis revealing up-regulated human epididymal protein-1 and down-regulated CL-100 in thyroid papillary carcinoma

TL;DR: It is shown that two-dimensional cDNA electrophoresis is a useful method of detecting differentially expressed genes in human diseases as demonstrated for HE-1 and CL-100 in papillary carcinoma.
References
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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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