2-hydroxypropyl- β-cyclodextrins and blood-brain barrier in Niemann-Pick Disease type C1

(Bentham Science Publishers) The rare, chronic, autosomal-recessive lysosomal storage disease Niemann-Pick disease type C1 (NPC1) is characterized by progressively debilitating and ultimately fatal neurological manifestations. There is an urgent need for disease-modifying therapies that address NPC1 neurological pathophysiology; and passage through the blood-brain barrier represents an important consideration for novel NPC1 drugs.
Source: EurekAlert! - Biology - Category: Biology Source Type: news

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Condition:   Niemann-Pick Disease, Type C Intervention:   Drug: VTS-270 Sponsor:   Vtesse, Inc., a Mallinckrodt Pharmaceuticals Company Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Plasmodium parasites possess a protein with homology to Niemann-Pick Type C1 proteins (Niemann-Pick Type C1-Related protein, NCR1). We isolated parasites with resistance-conferring mutations inPlasmodium falciparum NCR1 (PfNCR1) during selections with three diverse small-molecule antimalarial compounds and show that the mutations are causative for compound resistance. PfNCR1 protein knockdown results in severely attenuated growth and confers hypersensitivity to the compounds. Compound treatment or protein knockdown leads to increased sensitivity of the parasite plasma membrane (PPM) to the amphipathic glycoside saponin and...
Source: eLife - Category: Biomedical Science Tags: Microbiology and Infectious Disease Source Type: research
Source: Expert Opinion on Drug Discovery - Category: Drugs & Pharmacology Authors: Source Type: research
Conclusion: Taken together, increased intake of cereal fiber improved blood cholesterol profiles and increased the intestinal cholesterol efflux and cholesterol clearance in C57BL/6 mice fed a HFC diet. Oat fiber had a stronger effect than wheat bran fiber on cholesterol metabolism by modulating the PPARα, LXRα, and SREBP signaling pathways. PMID: 30863273 [PubMed]
Source: Food and Nutrition Research - Category: Nutrition Authors: Tags: Food Nutr Res Source Type: research
Abstract BACKGROUND: Niemann-Pick disease type C (NPC) is an autosomal recessive inherited disorder with progressive neuronal degeneration. Because conventional diagnostic methods are complicated and invasive, biomarker tests have drawn attention. We aimed to evaluate three urinary conjugated cholesterol metabolites as diagnostic biomarkers for NPC. METHODS: Urine samples from 23 patients with NPC, 28 healthy controls, and 7 patients with inherited metabolic disorders were analyzed. 3β-Sulfooxy-7β-N-acetylglucosaminyl-5-cholen-24-oic acid and its glycine and taurine conjugates in urine were quantifi...
Source: International Journal of Clinical Chemistry - Category: Chemistry Authors: Tags: Clin Chim Acta Source Type: research
. Cologna Niemann-Pick disease, type C1 (NPC1) is a rare, autosomal recessive, lipid storage disorder caused by mutations in NPC1. As a result, there is accumulation of unesterified cholesterol and sphingolipids in the late endosomal/lysosomal system. Clinically, patients can present with splenomegaly and hepatomegaly. In the current study, we analyzed the differential proteome of the spleen in symptomatic Npc1−/− mice to complement previous studies focused on the differential proteome of the liver, and then evaluated biomolecules that may serve as tissue biomarkers. The proteomic analysis revealed ...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Hypomyelination in the central nerves system (CNS) is one of the most obviously pathological features in Niemann-Pick Type C disease (NPC), which is a rare neurodegenerative disorder caused by mutations in the...
Source: Molecular Brain - Category: Neuroscience Authors: Tags: Research Source Type: research
Publication date: May 2019Source: Journal of Functional Foods, Volume 56Author(s): Shufen Han, Ru Zhang, Hui Gao, Jing Yang, Weiguo Zhang, Liqiang QinAbstractCardiovascular diseases caused by atherosclerosis have become one of the leading cause of death. The aim of the present study was to explore how oat fiber regulated lipid metabolism and to elucidate its anti-atherosclerotic potential in ApoE−/− mice. Animals were daily fed a high-fat diet without or with 0.8% oat fiber for 18 weeks. Both serum total cholesterol and low-density cholesterol levels decreased in mice received oat fiber administration than th...
Source: Journal of Functional Foods - Category: Nutrition Source Type: research
In this study we have used whole-body positron emission tomography (PET) and brain electronic autoradiography with copper-64 (64Cu), in the form of the copper(II) bis(thiosemicarbazonato) complex 64Cu-GTSM, to image short-term changes in copper trafficking after intravenous injection in a transgenic mouse model of NPC1 disease. 64Cu-GTSM is taken up in all tissues and dissociates rapidly inside cells, allowing monitoring of the subsequent efflux and redistribution of 64Cu from all tissues. Significantly enhanced retention of 64Cu radioactivity was observed in brain, lungs and blood at 15 h post-injection in symptomati...
Source: Biometals - Category: Biochemistry Authors: Tags: Biometals Source Type: research
Marceline Côté Filoviruses, such as Ebola virus (EBOV) and Marburg virus, are causative agents of unpredictable outbreaks of severe hemorrhagic fevers in humans and non-human primates. For infection, filoviral particles need to be internalized and delivered to intracellular vesicles containing cathepsin proteases and the viral receptor Niemann-Pick C1. Previous studies have shown that EBOV triggers macropinocytosis of the viral particles in a glycoprotein (GP)-dependent manner, but the molecular events required for filovirus internalization remain mostly unknown. Here we report that the diacylglycerol kina...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research
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