4,780 results match your criteria Pick Disease


Mitochondrial biogenesis is transcriptionally repressed in lysosomal lipid storage diseases.

Elife 2019 Feb 18;8. Epub 2019 Feb 18.

Institute of Cellular Biochemistry, University Medical Center Goettingen, Goettingen, Germany.

Perturbations in mitochondrial function and homeostasis are pervasive in lysosomal storage diseases, but the underlying mechanisms remain unknown. Here, we report a transcriptional program that represses mitochondrial biogenesis and function in lysosomal storage diseases Niemann-Pick type C (NPC) and acid sphingomyelinase deficiency (ASM), in patient cells and mouse tissues. This mechanism is mediated by the transcription factors KLF2 and ETV1, which are both induced in NPC and ASM patient cells. Read More

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http://dx.doi.org/10.7554/eLife.39598DOI Listing
February 2019
1 Read

Application of quercetin in neurological disorders: from nutrition to nanomedicine.

Rev Neurosci 2019 Feb 12. Epub 2019 Feb 12.

Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan 8174673441, Iran.

Quercetin is a polyphenolic flavonoid, which is frequently found in fruits and vegetables. The antioxidant potential of quercetin has been studied from subcellular compartments, that is, mitochondria to tissue levels in the brain. The neurodegeneration process initiates alongside aging of the neurons. Read More

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http://www.degruyter.com/view/j/revneuro.ahead-of-print/revn
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http://dx.doi.org/10.1515/revneuro-2018-0080DOI Listing
February 2019
7 Reads

Lysosomal storage disease overview.

Authors:
Angela Sun

Ann Transl Med 2018 Dec;6(24):476

Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.

The lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders that are caused for the most part by enzyme deficiencies within the lysosome resulting in accumulation of undegraded substrate. This storage process leads to a broad spectrum of clinical manifestations depending on the specific substrate and site of accumulation. Examples of LSDs include the mucopolysaccharidoses, mucolipidoses, oligosaccharidoses, Pompe disease, Gaucher disease, Fabry disease, the Niemann-Pick disorders, and neuronal ceroid lipofuscinoses. Read More

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http://dx.doi.org/10.21037/atm.2018.11.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331358PMC
December 2018
1 Read

A case of Niemann-Pick disease type C with neonatal liver failure initially diagnosed as neonatal hemochromatosis.

Brain Dev 2019 Feb 5. Epub 2019 Feb 5.

Division of Neurology, National Center for Child Health and Development, Tokyo, Japan.

Background: Niemann-Pick type C (NPC) is a lysosomal lipid storage disease with mutation of NPC1/NPC2 genes, which transport lipids in the endosome and lysosome, and various neurological symptoms. NPC patients also develop hepatosplenomegaly or liver disorder in the neonatal period, and 10% suffer severe liver failure. Neonatal hemochromatosis (NH) is a liver disorder characterized by hepatic and extrahepatic siderosis. Read More

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http://dx.doi.org/10.1016/j.braindev.2019.01.004DOI Listing
February 2019
1 Read

Lipid⁻Protein Interactions in Niemann⁻Pick Type C Disease: Insights from Molecular Modeling.

Int J Mol Sci 2019 Feb 7;20(3). Epub 2019 Feb 7.

School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9BH, UK.

The accumulation of lipids in the late endosomes and lysosomes of Niemann⁻Pick type C disease (NPCD) cells is a consequence of the dysfunction of one protein (usually NPC1) but induces dysfunction in many proteins. We used molecular docking to propose (a) that NPC1 exports not just cholesterol, but also sphingosine, (b) that the cholesterol sensitivity of big potassium channel (BK) can be traced to a previously unappreciated site on the channel's voltage sensor, (c) that transient receptor potential mucolipin 1 (TRPML1) inhibition by sphingomyelin is likely an indirect effect, and (d) that phosphoinositides are responsible for both the mislocalization of annexin A2 (AnxA2) and a soluble NSF (N-ethylmaleimide Sensitive Fusion) protein attachment receptor (SNARE) recycling defect. These results are set in the context of existing knowledge of NPCD to sketch an account of the endolysosomal pathology key to this disease. Read More

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http://dx.doi.org/10.3390/ijms20030717DOI Listing
February 2019
1 Read

A Novel Texture Extraction Technique with T1 Weighted MRI for the Classification of Alzheimer's Disease.

J Neurosci Methods 2019 Feb 5. Epub 2019 Feb 5.

Department of Computer Science and Engineering, Community College, Pondicherry University, Puducherry, India.

Background: As the medical images contain both superficial and imperceptible patterns, textures are successfully used as discriminant features for the detection of cancers, tumors, etc. NEW METHOD: Our algorithm selects the specific image blocks and computes the textures using the following steps: At first, the center image slice of the axes (sagittal, coronal and axial) is divided into small blocks and those which approximately resembles the regions of interest are marked. Then, all the marked blocks which are in the same location as in the center slice are collected from all the other slices, and the textures are computed per block on all the individual slices. Read More

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http://dx.doi.org/10.1016/j.jneumeth.2019.01.011DOI Listing
February 2019
1 Read

Dietary Energy Restriction Ameliorates Cognitive Impairment in a Mouse Model of Traumatic Brain Injury.

J Mol Neurosci 2019 Feb 8. Epub 2019 Feb 8.

Department of Anatomy and Anthropology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Traumatic brain injury (TBI) is one of the most common causes of neurological damage in young people. It was previously reported that dietary restriction, by either intermittent fasting (IF) or daily caloric restriction (CR), could protect neurons against dysfunction and degeneration in animal models of stroke and Parkinson's disease. Recently, several studies have shown that the protein Sirtuin 1 (SIRT1) plays a significant role in the induced neuroprotection following dietary restriction. Read More

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http://dx.doi.org/10.1007/s12031-019-01271-6DOI Listing
February 2019
2 Reads

Disease characteristics, prognosis and miglustat treatment effects on disease progression in patients with Niemann-Pick disease Type C: an international, multicenter, retrospective chart review.

Orphanet J Rare Dis 2019 Feb 7;14(1):32. Epub 2019 Feb 7.

Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.

Background: Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder characterized by progressive neurodegenerative symptomatology. The signs and symptoms of NP-C vary with age at disease onset, and available therapies are directed at alleviating symptoms and stabilizing disease progression. We report the characteristics and factors related to disease progression, and analyze the effect of miglustat treatment on disease progression and patient survival using NP-C disability scales. Read More

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http://dx.doi.org/10.1186/s13023-019-0996-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367842PMC
February 2019
1 Read

The atypical antipsychotic quetiapine induces hyperlipidemia by activating intestinal PXR signaling.

JCI Insight 2019 Feb 7;4(3). Epub 2019 Feb 7.

Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky, USA.

Quetiapine, one of the most prescribed atypical antipsychotics, has been associated with hyperlipidemia and an increased risk for cardiovascular disease in patients, but the underlying mechanisms remain unknown. Here, we identified quetiapine as a potent and selective agonist for pregnane X receptor (PXR), a key nuclear receptor that regulates xenobiotic metabolism in the liver and intestine. Recent studies have indicated that PXR also plays an important role in lipid homeostasis. Read More

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http://dx.doi.org/10.1172/jci.insight.125657DOI Listing
February 2019
1 Read

ROS Scavenger, Ebselen, Has No Preventive Effect in New Hearing Loss Model Using a Cholesterol-Chelating Agent.

J Audiol Otol 2019 Feb 8. Epub 2019 Feb 8.

Department of Otorhinolaryngology, Boramae Medical Center, Seoul Metropolitan Government-Seoul National University, Seoul, Korea.

Background And Objectives: The antioxidant ebselen will be able to limit or prevent the ototoxicity arising from 2-hydroxypropyl-β-cyclodextrin (HPβCD). Niemann-Pick Type C (NPC) disease is a disorder of lysosomal storage manifested in sphingolipidosis. Recently, it was noted that experimental use of HPβCD could partially resolve the symptoms in both animals and human patients. Read More

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http://dx.doi.org/10.7874/jao.2018.00255DOI Listing
February 2019
1 Read

Exploring the live birth rates of women living with HIV in British Columbia, Canada.

PLoS One 2019 6;14(2):e0211434. Epub 2019 Feb 6.

Women's Health Research Institute, British Columbia Women's Hospital, Vancouver, British Columbia, Canada.

Objective: To evaluate the birth rates of women living with HIV (WLWH) compared to the general population in British Columbia (BC), Canada.

Methods: We retrospectively reviewed clinical and population level surveillance data from 1997 to 2015. Live birth rates from 1997 to 2015 among WLWH aged 15-49 years were compared with those of all BC women. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211434PLOS
February 2019
2 Reads

[Intracellularly Degradable Polyrotaxanes for Therapeutic Applications].

Authors:
Atsushi Tamura

Yakugaku Zasshi 2019 ;139(2):143-155

Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU).

Recently, the application of β-cyclodextrins (β-CDs) as therapeutic agents has received considerable attention. β-CDs have been reported to have therapeutic effects on various diseases, such as Niemann-Pick type C (NPC) disease, a family of lysosomal storage disorders characterized by the lysosomal accumulation of cholesterol. To further improve the therapeutic efficacy of β-CDs, the use of β-CD-threaded polyrotaxanes (PRXs) has been proposed as a carrier of β-CDs for NPC disease. Read More

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http://dx.doi.org/10.1248/yakushi.18-00168-1DOI Listing
January 2019
1 Read

NPC intracellular cholesterol transporter 1 (NPC1)-mediated cholesterol export from lysosomes.

J Biol Chem 2019 Feb;294(5):1706-1709

From the Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305-5307

Low-density lipoprotein particles are taken up by cells and delivered to the lysosome where their cholesterol esters are cleaved off by acid lipase. The released, free cholesterol is then exported from lysosomes for cellular needs or storage. This article summarizes recent advances in our understanding of the molecular basis of cholesterol export from lysosomes. Read More

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http://dx.doi.org/10.1074/jbc.TM118.004165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364775PMC
February 2019
1 Read

Cyclodextrin triggers MCOLN1-dependent endo-lysosome secretion in Niemann-Pick type C cells.

J Lipid Res 2019 Feb 1. Epub 2019 Feb 1.

University of Geneva, Switzerland;

In specialized cell types, lysosome-related organelles support regulated secretory pathways, while in non-specialized cells, lysosomes can undergo fusion with the plasma membrane in response to a transient rise in cytosolic calcium. Recent evidence also indicates that lysosome secretion can be controlled transcriptionally and promote clearance in lysosome storage diseases. In addition, evidence is also accumulating that low concentrations of cyclodextrins reduce the cholesterol storage phenotype in cells and animals with the cholesterol storage disease Niemann-Pick type C, via an unknown mechanism. Read More

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http://dx.doi.org/10.1194/jlr.M089979DOI Listing
February 2019
1 Read

Comparison of different functional prediction scores using a gene-based permutation model for identifying cancer driver genes.

BMC Med Genomics 2019 Jan 31;12(Suppl 1):22. Epub 2019 Jan 31.

Human Genetics Center, UTHealth School of Public Health, Houston, TX, USA.

Background: Identifying cancer driver genes (CDG) is a crucial step in cancer genomic toward the advancement of precision medicine. However, driver gene discovery is a very challenging task because we are not only dealing with huge amount of data; but we are also faced with the complexity of the disease including the heterogeneity of background somatic mutation rate in each cancer patient. It is generally accepted that CDG harbor variants conferring growth advantage in the malignant cell and they are positively selected, which are critical to cancer development; whereas, non-driver genes harbor random mutations with no functional consequence on cancer. Read More

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http://dx.doi.org/10.1186/s12920-018-0452-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357357PMC
January 2019
1 Read

Accelerated, Dose escalated, Sequential Chemoradiotherapy in Non-small-cell lung cancer (ADSCaN): a protocol for a randomised phase II study.

BMJ Open 2019 Jan 29;9(1):e019903. Epub 2019 Jan 29.

Cancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.

Introduction: Lung cancer is the most common cause of cancer mortality in the UK, and non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Most patients present with inoperable disease; therefore, radiotherapy plays a major role in treatment. However, the majority of patients are not suitable for the gold standard treatment (concurrent chemoradiotherapy) due to performance status and comorbidities. Read More

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http://dx.doi.org/10.1136/bmjopen-2017-019903DOI Listing
January 2019
1 Read

Metabolic liver diseases presenting with neonatal cholestasis: at the crossroad between old and new paradigms.

Eur J Pediatr 2019 Jan 28. Epub 2019 Jan 28.

Pediatric Gastroenterology Unit, Centro Materno Infantil do Norte - CMIN, Centro Hospitalar Universitário do Porto, Largo da Maternidade de Júlio Dinis, 4050-651, Porto, Portugal.

Metabolic liver diseases (MLD) are an important group of disorders presenting with neonatal cholestasis (NC). The spectrum of liver involvement is wide and the presumptive diagnosis is traditionally based on clinical and laboratory findings. Recently, next-generation sequencing (NGS) panels have emerged as an appealing tool to diagnose neonatal/infantile cholestatic disorders. Read More

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http://dx.doi.org/10.1007/s00431-019-03328-5DOI Listing
January 2019
1 Read

Imaging of tau deposits in adults with Niemann-Pick type C disease: a case-control study.

Eur J Nucl Med Mol Imaging 2019 Jan 28. Epub 2019 Jan 28.

The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia.

Purpose: Niemann-Pick type C (NPC) is a cholesterol storage disease characterized by disruption in the endosomal-lysosomal transport system that leads to the accumulation of cholesterol and glycolipids in lysosomes. Developmental cognitive delay and progressive motor and cognitive impairment are characteristic of the disease. Tau accumulation has been reported in some NPC patients. Read More

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http://dx.doi.org/10.1007/s00259-019-4273-7DOI Listing
January 2019
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Inhibition of Niemann-Pick C1-Like 1 by Ezetimibe Reduces Dietary 5β,6β-Epoxycholesterol Absorption in Rats.

Cardiovasc Drugs Ther 2019 Jan 22. Epub 2019 Jan 22.

Laboratory of Nutrition Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.

Purpose: Oxycholesterols (OCs) are produced from cholesterol by oxidation of the steroidal backbone and side-chain. OCs are present in blood and evidence suggests their involvement in disease development and progression. However, limited information is available regarding the absorption mechanisms and relative absorption rates of dietary OCs. Read More

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http://link.springer.com/10.1007/s10557-019-06854-4
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http://dx.doi.org/10.1007/s10557-019-06854-4DOI Listing
January 2019
3 Reads

Pneumococcal Immunization Reduces Neurological and Hepatic Symptoms in a Mouse Model for Niemann-Pick Type C1 Disease.

Front Immunol 2018 7;9:3089. Epub 2019 Jan 7.

Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands.

Niemann-Pick type C1 (NPC1) disease is caused by a deleterious mutation in the gene, causing lysosomal accumulation of unesterified cholesterol and sphingolipids. Consequently, NPC1 disease patients suffer from severe neurovisceral symptoms which, in the absence of effective treatments, result in premature death. NPC1 disease patients display increased plasma levels of cholesterol oxidation products such as those enriched in oxidized low-density lipoprotein (oxLDL), a pro-inflammatory mediator. Read More

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http://dx.doi.org/10.3389/fimmu.2018.03089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330339PMC
January 2019
1 Read

Recommendations for patient screening in ultra-rare inherited metabolic diseases: what have we learned from Niemann-Pick disease type C?

Orphanet J Rare Dis 2019 Jan 21;14(1):20. Epub 2019 Jan 21.

University of Pretoria, Pretoria, South Africa.

Background: Rare and ultra-rare diseases (URDs) are often chronic and life-threatening conditions that have a profound impact on sufferers and their families, but many are notoriously difficult to detect. Niemann-Pick disease type C (NP-C) serves to illustrate the challenges, benefits and pitfalls associated with screening for ultra-rare inborn errors of metabolism (IEMs). A comprehensive, non-systematic review of published information from NP-C screening studies was conducted, focusing on diagnostic methods and study designs that have been employed to date. Read More

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http://dx.doi.org/10.1186/s13023-018-0985-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341610PMC
January 2019
1 Read

Molecular Pathways and Respiratory Involvement in Lysosomal Storage Diseases.

Int J Mol Sci 2019 Jan 15;20(2). Epub 2019 Jan 15.

Rare Metabolic Diseases Unit, Pediatric Department, Fondazione MBBM, Università degli Studi di Milano Bicocca, San Gerardo Hospital, ASST di Monza, 20900 Monza, Italy.

Lysosomal storage diseases (LSD) include a wide range of different disorders with variable degrees of respiratory system involvement. The purpose of this narrative review is to treat the different types of respiratory manifestations in LSD, with particular attention being paid to the main molecular pathways known so far to be involved in the pathogenesis of the disease. A literature search was conducted using the Medline/PubMed and EMBASE databases to identify studies, from 1968 through to November 2018, that investigated the respiratory manifestations and molecular pathways affected in LSD. Read More

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http://dx.doi.org/10.3390/ijms20020327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359090PMC
January 2019
1 Read

Trends in cause-specific mortality in HIV-Hepatitis C co-infection following hepatitis C treatment scale-up.

AIDS 2019 Jan 12. Epub 2019 Jan 12.

Department of Medicine, Division of Infectious Diseases and Chronic Viral Illness Service, McGill University, Montreal, Quebec, Canada.

Objective: Hepatitis C virus (HCV) treatment may reduce liver-related mortality but with competing risks, other causes of mortality may undermine benefits. We examined changes in cause-specific mortality among HIV-HCV co-infected patients before and after scale-up of HCV treatment.

Design: Prospective multicentre HIV-HCV cohort study in Canada. Read More

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http://dx.doi.org/10.1097/QAD.0000000000002156DOI Listing
January 2019
6 Reads

Midkine drives cardiac inflammation by promoting neutrophil trafficking and NETosis in myocarditis.

J Exp Med 2019 Feb 15;216(2):350-368. Epub 2019 Jan 15.

Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-University Munich, Planegg-Martinsried, Germany

Heart failure due to dilated cardiomyopathy is frequently caused by myocarditis. However, the pathogenesis of myocarditis remains incompletely understood. Here, we report the presence of neutrophil extracellular traps (NETs) in cardiac tissue of patients and mice with myocarditis. Read More

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http://www.jem.org/lookup/doi/10.1084/jem.20181102
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http://dx.doi.org/10.1084/jem.20181102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363424PMC
February 2019
7 Reads
12.515 Impact Factor

Is autophagy an elective strategy to protect neurons from dysregulated cholesterol metabolism?

Neural Regen Res 2019 Apr;14(4):582-587

Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.

The balance of autophagy, apoptosis and necroptosis is crucial to determine the outcome of the cellular response to cholesterol dysregulation. Cholesterol plays a major role in regulating the properties of cell membranes, especially as regards their fluidity, and the regulation of its biosynthesis influences the shape and functions of these membranes. Whilst dietary cholesterol can easily be distributed to most organs, the central nervous system, whose membranes are particularly rich in cholesterol, mainly relies on de novo synthesis. Read More

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http://www.nrronline.org/text.asp?2019/14/4/582/247441
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http://dx.doi.org/10.4103/1673-5374.247441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352582PMC
April 2019
19 Reads

Psychiatric and Cognitive Symptoms Associated with Niemann-Pick Type C Disease: Neurobiology and Management.

CNS Drugs 2019 Feb;33(2):125-142

Neuropsychiatry Unit, The Royal Melbourne Hospital, Melbourne, VIC, Australia.

Niemann-Pick disease type C (NPC) is a lysosomal storage disorder that presents with a spectrum of clinical manifestations from infancy and childhood or in early or mid-adulthood. Progressive neurological symptoms including ataxia, dystonia and vertical gaze palsy are a hallmark of the disease, and psychiatric symptoms such as psychosis and mood disorders are common. These latter symptoms often present early in the course of NPC and thus these patients are often diagnosed with a major psychotic or affective disorder before neurological and cognitive signs present and the diagnosis is revised. Read More

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http://link.springer.com/10.1007/s40263-018-0599-0
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http://dx.doi.org/10.1007/s40263-018-0599-0DOI Listing
February 2019
11 Reads

Defects in sarcolemma repair and skeletal muscle function after injury in a mouse model of Niemann-Pick type A/B disease.

Skelet Muscle 2019 Jan 5;9(1). Epub 2019 Jan 5.

Department of Cell Biology and Molecular Genetics, University of Maryland, 2134 Bioscience Research Building, College Park, MD, 20742-5815, USA.

Background: Niemann-Pick disease type A (NPDA), a disease caused by mutations in acid sphingomyelinase (ASM), involves severe neurodegeneration and early death. Intracellular lipid accumulation and plasma membrane alterations are implicated in the pathology. ASM is also linked to the mechanism of plasma membrane repair, so we investigated the impact of ASM deficiency in skeletal muscle, a tissue that undergoes frequent cycles of injury and repair in vivo. Read More

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https://skeletalmusclejournal.biomedcentral.com/articles/10.
Publisher Site
http://dx.doi.org/10.1186/s13395-018-0187-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320626PMC
January 2019
3 Reads

Implementing a community vector collection strategy using xenomonitoring for the endgame of lymphatic filariasis elimination.

Parasit Vectors 2018 Dec 27;11(1):672. Epub 2018 Dec 27.

Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.

Background: The global strategy for elimination of lymphatic filariasis is by annual mass drug administration (MDA). Effective implementation of this strategy in endemic areas reduces Wuchereria bancrofti in the blood of infected individuals to very low levels. This minimises the rate at which vectors successfully pick microfilariae from infected blood, hence requiring large mosquito numbers to detect infections. Read More

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http://dx.doi.org/10.1186/s13071-018-3260-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307201PMC
December 2018
1 Read
3.430 Impact Factor

DR-region of Na/K ATPase is a target to treat excitotoxicity and stroke.

Cell Death Dis 2018 Dec 18;10(1). Epub 2018 Dec 18.

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.

Na/K ATPase (NKA) is important in maintaining cellular functions. We found that loss of NKA activities in NKAα1 mice is associated with increased susceptibility to ischemic injuries following transient middle cerebral artery occlusion (tMCAO). This is corroborated by the neuroprotective effects of an antibody raised against an extracellular DR region (DVEDSYGQQWTYEQR, sequence number as in rat) of NKAα subunit (DR-Ab) in both preventive and therapeutic settings. Read More

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http://dx.doi.org/10.1038/s41419-018-1230-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315034PMC
December 2018
1 Read

Seeding selectivity and ultrasensitive detection of tau aggregate conformers of Alzheimer disease.

Acta Neuropathol 2018 Dec 20. Epub 2018 Dec 20.

LPVD, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, 59840, USA.

Alzheimer disease (AD) and chronic traumatic encephalopathy (CTE) involve the abnormal accumulation in the brain of filaments composed of both three-repeat (3R) and four-repeat (4R) (3R/4R) tau isoforms. To probe the molecular basis for AD's tau filament propagation and to improve detection of tau aggregates as potential biomarkers, we have exploited the seeded polymerization growth mechanism of tau filaments to develop a highly selective and ultrasensitive cell-free tau seed amplification assay optimized for AD (AD real-time quaking-induced conversion or AD RT-QuIC). The reaction is based on the ability of AD tau aggregates to seed the formation of amyloid fibrils made of certain recombinant tau fragments. Read More

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http://dx.doi.org/10.1007/s00401-018-1947-3DOI Listing
December 2018
4 Reads

Enrichment of pathogenic variants in genes associated with inborn errors of metabolism in psychiatric populations.

Am J Med Genet B Neuropsychiatr Genet 2019 Jan 16;180(1):46-54. Epub 2018 Dec 16.

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Many genetic conditions can mimic mental health disorders, with psychiatric symptoms that are difficult to treat with standard psychotropic medications. This study tests the hypothesis that psychiatric populations are enriched for pathogenic variants associated with selected inborn errors of metabolism (IEMs). Using next-generation sequencing, 2046 psychiatric patients were screened for pathogenic variants in genes associated with four IEMs, Niemann-Pick disease type C (NPC), Wilson disease (WD), homocystinuria (HOM), and acute intermittent porphyria (AIP). Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.b.32702
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http://dx.doi.org/10.1002/ajmg.b.32702DOI Listing
January 2019
8 Reads

A study in a Polish ataxia cohort indicates genetic heterogeneity and points to MTCL1 as a novel candidate gene.

Clin Genet 2019 Mar 8;95(3):415-419. Epub 2019 Jan 8.

Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.

Inherited ataxias are a group of highly heterogeneous, complex neurological disorders representing a significant diagnostic challenge in clinical practice. We performed a next-generation sequencing (NGS) analysis in 10 index cases with unexplained progressive cerebellar ataxia of suspected autosomal recessive inheritance. A definite molecular diagnosis was obtained in 5/10 families and included the following diseases: autosomal recessive spastic ataxia of Charlevoix-Saguenay, POLR3B-related hypomyelinating leukodystrophy, primary coenzyme Q10 deficiency type 4, Niemann-Pick disease type C1 and SYNE1-related ataxia. Read More

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http://dx.doi.org/10.1111/cge.13489DOI Listing
March 2019
14 Reads

Lipid-induced lysosomal damage after demyelination corrupts microglia protective function in lysosomal storage disorders.

EMBO J 2019 Jan 7;38(2). Epub 2018 Dec 7.

Department of Molecular Neuropathology, Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Madrid, Spain

Neuropathic lysosomal storage disorders (LSDs) present with activated pro-inflammatory microglia. However, anti-inflammatory treatment failed to improve disease pathology. We characterise the mechanisms underlying microglia activation in Niemann-Pick disease type A (NPA). Read More

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http://dx.doi.org/10.15252/embj.201899553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331723PMC
January 2019
3 Reads
10.434 Impact Factor

Radiochemical synthesis and preclinical evaluation of Ga-labeled NODAGA-hydroxypropyl-beta-cyclodextrin (Ga-NODAGA-HPBCD).

Eur J Pharm Sci 2019 Feb 4;128:202-208. Epub 2018 Dec 4.

Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary. Electronic address:

A new renaissance started in the research and application of cyclodextrins a few years ago. 2-Hydroxypropyl-beta-cyclodextrin (HPBCD) is used in the formulation of drugs and recently orphan designation was granted for the treatment of Niemann-Pick disease, type C. HPBCD is considered to be safe, but the exact mechanism of action and side effects are not completely explained. Read More

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http://dx.doi.org/10.1016/j.ejps.2018.12.001DOI Listing
February 2019
3 Reads

A DNA nanomachine chemically resolves lysosomes in live cells.

Nat Nanotechnol 2019 Feb 3;14(2):176-183. Epub 2018 Dec 3.

Department of Chemistry, The University of Chicago, Chicago, IL, USA.

Lysosomes are multifunctional, subcellular organelles with roles in plasma membrane repair, autophagy, pathogen degradation and nutrient sensing. Dysfunctional lysosomes underlie Alzheimer's disease, Parkinson's disease and rare lysosomal storage diseases, but their contributions to these pathophysiologies are unclear. Live imaging has revealed lysosome subpopulations with different physical characteristics including dynamics, morphology or cellular localization. Read More

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http://dx.doi.org/10.1038/s41565-018-0318-5DOI Listing
February 2019
6 Reads

Exploring the Therapeutic Landscape of Sphingomyelinases.

Handb Exp Pharmacol 2018 Nov 27. Epub 2018 Nov 27.

Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, USA.

Sphingosine, ceramide, sphingosine-1-phosphate, and other related sphingolipids have emerged as important bioactive molecules involved in a variety of key cellular processes such as cell growth, differentiation, apoptosis, exosome release, and inter- and intracellular cell communication, making the pathways of sphingolipid metabolism a key domain in maintaining cell homeostasis (Hannun and Obeid, Trends Biochem Sci 20:73-77, 1995; Hannun and Obeid, Nat Rev Mol Cell Biol 9:139-150, 2008; Kosaka et al., J Biol Chem 288:10849-10859, 2013). Various studies have determined that these pathways play a central role in regulating intracellular production of ceramide and the other bioactive sphingolipids and hence are an important component of signaling in various diseases such as cancer, diabetes, and neurodegenerative and cardiovascular diseases (Chaube et al. Read More

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http://dx.doi.org/10.1007/164_2018_179DOI Listing
November 2018
3 Reads

Pharmacokinetics and efficacy of PT302, a sustained-release Exenatide formulation, in a murine model of mild traumatic brain injury.

Neurobiol Dis 2019 Apr 22;124:439-453. Epub 2018 Nov 22.

Drug Design and Development Section, Translational Gerontology Branch, Intramural Research Program, National Institutes of Health, National Institute on Aging, Baltimore, MD, USA; Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.

Traumatic brain injury (TBI) is a neurodegenerative disorder for which no effective pharmacological treatment is available. Glucagon-like peptide 1 (GLP-1) analogues such as Exenatide have previously demonstrated neurotrophic and neuroprotective effects in cellular and animal models of TBI. However, chronic or repeated administration was needed for efficacy. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09699961183066
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http://dx.doi.org/10.1016/j.nbd.2018.11.023DOI Listing
April 2019
14 Reads

Gadolinium Chloride Rescues Niemann⁻Pick Type C Liver Damage.

Int J Mol Sci 2018 Nov 14;19(11). Epub 2018 Nov 14.

Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile.

Niemann⁻Pick type C (NPC) disease is a rare neurovisceral cholesterol storage disorder that arises from loss of function mutations in the or genes. Soon after birth, some patients present with an aggressive hepatosplenomegaly and cholestatic signs. Histopathologically, the liver presents with large numbers of foam cells; however, their role in disease pathogenesis has not been explored in depth. Read More

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http://dx.doi.org/10.3390/ijms19113599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274821PMC
November 2018
3 Reads

Early fetal echocardiography.

Birth Defects Res 2018 Nov 14. Epub 2018 Nov 14.

Fetal & Neonatal Cardiology Program, Division of Cardiology, Department of Pediatrics, Stollery Children's Hospital, Edmonton, Alberta, Canada.

Objectives: To explore the technical aspects and clinical utility of early fetal echocardiography and screening of the fetal heart in early pregnancy. Also, to document differences in cardiac structure and function which can be demonstrated in the late first/early second trimesters.

Methods: In addition to summarizing our own experiences of late first/early second trimester fetal echocardiography, we reviewed the literature to explore clinical indications for, technical aspects, safety, accuracy, strengths and weaknesses of early fetal echocardiography. Read More

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http://doi.wiley.com/10.1002/bdr2.1414
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http://dx.doi.org/10.1002/bdr2.1414DOI Listing
November 2018
16 Reads

Stem cell-secreted 14,15- epoxyeicosatrienoic acid rescues cholesterol homeostasis and autophagic flux in Niemann-Pick-type C disease.

Exp Mol Med 2018 Nov 14;50(11):149. Epub 2018 Nov 14.

Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, 08826, South Korea.

We previously demonstrated that the direct transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the dentate gyrus ameliorated the neurological symptoms of Niemann-Pick type C1 (NPC1)-mutant mice. However, the clinical presentation of NPC1-mutant mice was not fully understood with a molecular mechanism. Here, we found 14,15-epoxyeicosatrienoic acid (14,15-EET), a cytochrome P450 (CYP) metabolite, from hUCB-MSCs and the cerebella of NPC1-mutant mice and investigated the functional consequence of this metabolite. Read More

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http://www.nature.com/articles/s12276-018-0176-0
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http://dx.doi.org/10.1038/s12276-018-0176-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235958PMC
November 2018
10 Reads

Main Olfactory and Vomeronasal Epithelium Are Differently Affected in Niemann-Pick Disease Type C1.

Int J Mol Sci 2018 Nov 12;19(11). Epub 2018 Nov 12.

Department of Anatomy, University of Rostock, 18057 Rostock, Germany.

Introduction: Olfactory impairment is one of the earliest symptoms in neurodegenerative disorders that has also been documented in Niemann-Pick disease type C1 (NPC1). NPC1 is a very rare, neurovisceral lipid storage disorder, characterized by a deficiency of gene function that leads to progressive neurodegeneration. Here, we compared the pathologic effect of defective gene on the vomeronasal neuroepithelium (VNE) with that of the olfactory epithelium (OE) in an NPC1 mouse model. Read More

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http://www.mdpi.com/1422-0067/19/11/3563
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http://dx.doi.org/10.3390/ijms19113563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274921PMC
November 2018
9 Reads

Lung transplantation in a patient with Niemann-Pick disease.

J Heart Lung Transplant 2019 Jan 16;38(1):100-101. Epub 2018 Oct 16.

Division of Pulmonary and Critical Care Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA.

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https://linkinghub.elsevier.com/retrieve/pii/S10532498183170
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http://dx.doi.org/10.1016/j.healun.2018.10.002DOI Listing
January 2019
13 Reads

Necroptosis inhibition as a therapy for Niemann-Pick disease, type C1: Inhibition of RIP kinases and combination therapy with 2-hydroxypropyl-β-cyclodextrin.

Mol Genet Metab 2018 Dec 30;125(4):345-350. Epub 2018 Oct 30.

Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, DHHS, Bethesda, MD 20892, USA. Electronic address:

Niemann-Pick disease, type C1 (NPC1) is an inborn error of metabolism that results in endolysosomal accumulation of unesterified cholesterol. Clinically, NPC1 manifests as cholestatic liver disease in the newborn or as a progressive neurogenerative condition characterized by cerebellar ataxia and cognitive decline. Currently there are no FDA approved therapies for NPC1. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192183054
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http://dx.doi.org/10.1016/j.ymgme.2018.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279611PMC
December 2018
13 Reads

Eugenol-hyperactivated nymphs of Triatoma infestans become intoxicated faster than non-hyperactivated nymphs when exposed to a permethrin-treated surface.

Parasit Vectors 2018 Nov 3;11(1):573. Epub 2018 Nov 3.

UNIDEF-CITEDEF-CONICET- CIPEIN, Juan B. de La Salle 4397, (1603) Villa Martelli, Buenos Aires, Argentina.

Background: Eugenol is a botanical monoterpene that hyperactivates the blood-sucking bug Triatoma infestans, and permethrin is a pyrethroid with a strong triatomicide effect. In the present work, we tested the hypothesis that eugenol-hyperactivated nymphs of T. infestans pick up more insecticide, and then become intoxicated faster, than non-hyperactivated nymphs when exposed to a permethrin-treated surface. Read More

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http://dx.doi.org/10.1186/s13071-018-3146-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215654PMC
November 2018
2 Reads

Activation of mammalian terget of rapamycin kinase and glycogen synthase kinase-3β accompanies abnormal accumulation of cholesterol in fibroblasts from Niemann-Pick type C patients.

J Cell Biochem 2019 Apr 2;120(4):6580-6588. Epub 2018 Nov 2.

Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.

Background: Niemann Pick type C (NPC) lysosomal disorder is linked to the disruption of cholesterol transport. Recent data suggest that the molecular background of this disease is more complex. It was found that accumulation of cholesterol and glycolipids in the late endosomal/lysosomal compartment of NPC1 cells may affect mitochondrial functions. Read More

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http://doi.wiley.com/10.1002/jcb.27951
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http://dx.doi.org/10.1002/jcb.27951DOI Listing
April 2019
5 Reads

A case series of hereditary cerebellar ataxias in a highly consanguineous population from Northeast Brazil.

Parkinsonism Relat Disord 2018 Oct 26. Epub 2018 Oct 26.

Division of Neurology, Department of Clinical Medicine, Universidade Federal do Ceará, Brazil; Neurology Service, Hospital Geral de Fortaleza, Fortaleza, Ceará, Brazil; Center of Health Sciences, Universidade Estadual do Ceará, Brazil. Electronic address:

Background: There are few studies reporting characteristics of patients with cerebellar ataxias in the Brazilian population. The aim of this study was to provide a detailed neurological description of patients with hereditary ataxia followed by a neurology outpatient service in Brazil.

Methods: Neurological and clinical evaluation of patients with hereditary ataxia was performed at a neurology service outpatient clinic of a hospital in Northeast Brazil between October 2013 and January 2015. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S13538020183046
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http://dx.doi.org/10.1016/j.parkreldis.2018.10.027DOI Listing
October 2018
20 Reads

Familial Hypercholesterolemia: The Most Frequent Cholesterol Metabolism Disorder Caused Disease.

Int J Mol Sci 2018 Nov 1;19(11). Epub 2018 Nov 1.

Departamento de Bioquímica, Instituto Biofisika (UPV/EHU, CSIC), Universidad del País Vasco, Apdo.644, 48080 Bilbao, Spain.

Cholesterol is an essential component of cell barrier formation and signaling transduction involved in many essential physiologic processes. For this reason, cholesterol metabolism must be tightly controlled. Cell cholesterol is mainly acquired from two sources: Dietary cholesterol, which is absorbed in the intestine and, intracellularly synthesized cholesterol that is mainly synthesized in the liver. Read More

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http://www.mdpi.com/1422-0067/19/11/3426
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http://dx.doi.org/10.3390/ijms19113426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275065PMC
November 2018
7 Reads

Effect of valaciclovir on CD4 count decline in untreated HIV: an international randomized controlled trial.

J Antimicrob Chemother 2019 Feb;74(2):480-488

Department of Medicine, University of Toronto, Toronto, Canada.

Objectives: To determine the impact of valaciclovir on HIV disease progression in treatment-naive HIV-positive adults.

Methods: In this fully blind, multicentre, 1:1 randomized placebo-controlled trial, treatment-naive HIV-1-positive adults with CD4 counts 400-900 cells/mm3 and not meeting contemporaneous recommendations for combination ART (cART) were randomized to valaciclovir 500 mg or placebo twice daily, and followed quarterly until having two consecutive CD4 counts ≤350 cells/mm3 or initiating cART for any reason. The primary analysis compared the rate of CD4 count decline by study arm after adjusting for baseline CD4 count and viral load (VL). Read More

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https://academic.oup.com/jac/advance-article/doi/10.1093/jac
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http://dx.doi.org/10.1093/jac/dky433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337901PMC
February 2019
15 Reads

Cyclodextrins reduce the ability of Pseudomonas aeruginosa outer-membrane vesicles to reduce CFTR Cl secretion.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 25;316(1):L206-L215. Epub 2018 Oct 25.

Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.

Pseudomonas aeruginosa secretes outer-membrane vesicles (OMVs) that fuse with cholesterol-rich lipid rafts in the apical membrane of airway epithelial cells and decrease wt-CFTR Cl secretion. Herein, we tested the hypothesis that a reduction of the cholesterol content of CF human airway epithelial cells by cyclodextrins reduces the inhibitory effect of OMVs on VX-809 (lumacaftor)-stimulated Phe508del CFTR Cl secretion. Primary CF bronchial epithelial cells and CFBE cells were treated with vehicle, hydroxypropyl-β-cyclodextrin (HPβCD), or methyl-β-cyclodextrin (MβCD), and the effects of OMVs secreted by P. Read More

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https://www.physiology.org/doi/10.1152/ajplung.00316.2018
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http://dx.doi.org/10.1152/ajplung.00316.2018DOI Listing
January 2019
18 Reads