keyword
MENU ▼
Read by QxMD icon Read
search

Niemann-pick

keyword
https://www.readbyqxmd.com/read/29904147/dpubchem-a-web-tool-for-qsar-modeling-and-high-throughput-virtual-screening
#1
Othman Soufan, Wail Ba-Alawi, Arturo Magana-Mora, Magbubah Essack, Vladimir B Bajic
High-throughput screening (HTS) performs the experimental testing of a large number of chemical compounds aiming to identify those active in the considered assay. Alternatively, faster and cheaper methods of large-scale virtual screening are performed computationally through quantitative structure-activity relationship (QSAR) models. However, the vast amount of available HTS heterogeneous data and the imbalanced ratio of active to inactive compounds in an assay make this a challenging problem. Although different QSAR models have been proposed, they have certain limitations, e...
June 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29903436/the-neuropathology-of-the-adult-cerebellum
#2
Arnulf H Koeppen
This chapter summarizes the neuropathologic features of nonneoplastic disorders of the adult cerebellum. Gait ataxia and extremity dysmetria are clinical manifestations of diseases that interrupt the complex cerebellar circuitry between the neurons of the cerebellar cortex, the cerebellar nuclei (especially the dentate nuclei), and the inferior olivary nuclei. The cerebellum is a prominent target of several sporadic and hereditary neurodegenerative diseases, including multiple system atrophy, spinocerebellar ataxia, and Friedreich ataxia...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29900534/absence-of-infiltrating-peripheral-myeloid-cells-in-the-brains-of-mouse-models-of-lysosomal-storage-disorders
#3
REVIEW
Soo Min Cho, Ayelet Vardi, Nicolas Platt, Anthony H Futerman
Approximately 70 lysosomal storage diseases are currently known, resulting from mutations in genes encoding lysosomal enzymes and membrane proteins. Defects in lysosomal enzymes that hydrolyze sphingolipids have been relatively well studied. Gaucher disease is caused by the loss of activity of glucocerebrosidase, leading to accumulation of glucosylceramide. Gaucher disease exhibits a number of subtypes, with types 2 and 3 showing significant neuropathology. Sandhoff disease results from the defective activity of β-hexosaminidase, leading to accumulation of ganglioside GM2...
June 14, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29899496/transcriptional-control-of-intestinal-cholesterol-absorption-adipose-energy-expenditure-and-lipid-handling-by-sortilin
#4
Sumihiko Hagita, Maximillian A Rogers, Tan Pham, Jennifer R Wen, Andrew K Mlynarchik, Masanori Aikawa, Elena Aikawa
The sorting receptor Sortilin functions in the regulation of glucose and lipid metabolism. Dysfunctional lipid uptake, storage, and metabolism contribute to several major human diseases including atherosclerosis and obesity. Sortilin associates with cardiovascular disease; however, the role of Sortilin in adipose tissue and lipid metabolism remains unclear. Here we show that in the low-density lipoprotein receptor-deficient (Ldlr-/- ) atherosclerosis model, Sortilin deficiency (Sort1-/- ) in female mice suppresses Niemann-Pick type C1-Like 1 (Npc1l1) mRNA levels, reduces body and white adipose tissue weight, and improves brown adipose tissue function partially via transcriptional downregulation of Krüppel-like factor 4 and Liver X receptor...
June 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29897878/model-construction-of-niemann-pick-type-c-disease-in-zebrafish
#5
Yusheng Lin, Xiaolian Caia, Guiping Wang, Gang Ouyang, Hong Cao
Niemann-Pick Type C disease (NPC) is a rare human disease, with limited effective treatment options. Most cases of NPC disease are associated with inactivating mutations of the NPC1 gene. However, cellular and molecular mechanisms responsible for the NPC1 pathogenesis remain poorly defined. This is partly due to the lack of a suitable animal model to monitor the disease progression. In this study, we used CRISPR to construct an NPC1-/- zebrafish model, which faithfully reproduced the cardinal pathological features of this disease...
June 1, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29886186/a-foreleg-transcriptome-for-ixodes-scapularis-ticks-candidates-for-chemoreceptors-and-binding-proteins-that-might-be-expressed-in-the-sensory-haller-s-organ
#6
Tanya Josek, Kimberly K O Walden, Brian F Allan, Marianne Alleyne, Hugh M Robertson
Little is known about the molecular basis for the olfactory capabilities of the sensory Haller's organ on the forelegs of ticks. We first expanded the known repertoire of Ionotropic Receptors (IRs), a variant lineage of the ionotropic glutamate receptors, encoded by the black-legged Ixodes scapularis genome from 15 to 125. We then undertook a transcriptome study of fore- and hind-legs of this tick in an effort to identify candidate chemoreceptors differentially expressed in forelegs as likely to be involved in Haller's organ functions...
May 26, 2018: Ticks and Tick-borne Diseases
https://www.readbyqxmd.com/read/29878847/niemann-pick-c1-deficient-mice-lacking-sterol-o-acyltransferase-2-have-less-hepatic-cholesterol-entrapment-and-improved-liver-function
#7
Adam M Lopez, Ryan Dale Jones, Joyce J Repa, Stephen D Turley
Cholesteryl esters are generated at multiple sites in the body by sterol O-acyltransferase 1 (SOAT1) or sterol O-acyltransferase 2 (SOAT2) in various cell types, and lecithin cholesterol acyltransferase (LCAT) in plasma. Esterified cholesterol (EC) and triacylglycerol (TAG) contained in lipoproteins cleared from the circulation via receptor-mediated or bulk-phase endocytosis are hydrolyzed by lysosomal acid lipase (LAL) within the late endosomal/lysosomal (E/L) compartment. Then, through the successive actions of Niemann-Pick C2 (NPC2) and Niemann-Pick C1 (NPC1), unesterified cholesterol (UC) is exported from the E/L compartment to the cytosol...
June 7, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29878115/aav9-intracerebroventricular-gene-therapy-improves-lifespan-locomotor-function-and-pathology-in-a-mouse-model-of-niemann-pick-type-c1-disease
#8
Michael P Hughes, Dave A Smith, Lauren Morris, Claire Fletcher, Alexandria Colaco, Mylene Huebecker, Julie Tordo, Nuria Palomar, Giulia Massaro, Els Henckaerts, Simon N Waddington, Frances M Platt, Ahad A Rahim
Niemann-Pick type C disease (NP-C) is a fatal neurodegenerative lysosomal storage disorder. It is caused in 95% of cases by a mutation in the NPC1 gene that encodes NPC1, an integral transmembrane protein localised to the limiting membrane of the lysosome. There is no cure for NP-C but there is a disease-modifying drug (miglustat) that slows disease progression but with associated side effects. Here, we demonstrate in a well-characterised mouse model of NP-C that a single administration of AAV-mediated gene therapy to the brain can significantly extend lifespan, improve quality of life, prevent or ameliorate neurodegeneration, reduce biochemical pathology and normalize or improve various indices of motor function...
June 5, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29874879/niemann-pick-type-c2-protein-regulates-free-cholesterol-accumulation-and-influences-hepatic-stellate-cell-proliferation-and-mitochondrial-respiration-function
#9
Yuan-Hsi Wang, Yuh-Ching Twu, Chung-Kwe Wang, Fu-Zhen Lin, Chun-Ya Lee, Yi-Jen Liao
Liver fibrosis is the first step toward the progression to cirrhosis, portal hypertension, and hepatocellular carcinoma. A high-cholesterol diet is associated with liver fibrosis via the accumulation of free cholesterol in hepatic stellate cells (HSCs). Niemann-Pick type C2 (NPC2) plays an important role in the regulation of intracellular free cholesterol homeostasis via direct binding with free cholesterol. Previously, we reported that NPC2 was downregulated in liver cirrhosis tissues. Loss of NPC2 enhanced the accumulation of free cholesterol in HSCs and made them more susceptible to transforming growth factor (TGF)-β1...
June 5, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29871644/distinguishing-neurocognitive-deficits-in-adult-patients-with-np-c-from-early-onset-alzheimer-s-dementia
#10
Andreas Johnen, Matthias Pawlowski, Thomas Duning
BACKGROUND: Niemann-Pick disease type C (NP-C) is a rare, progressive neurodegenerative disease caused by mutations in the NPC1 or the NPC2 gene. Neurocognitive deficits are common in NP-C, particularly in patients with the adolescent/adult-onset form. As a disease-specific therapy is available, it is important to distinguish clinically between the cognitive profiles in NP-C and primary dementia (e.g., early Alzheimer's disease; eAD). METHODS: In a prospective observational study, we directly compared the neurocognitive profiles of patients with confirmed NP-C (n = 7) and eAD (n = 15)...
June 5, 2018: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/29862881/cholesterol-impairs-autophagy-mediated-clearance-of-amyloid-beta-while-promoting-its-secretion
#11
Elisabet Barbero-Camps, Vicente Roca-Agujetas, Isabel Bartolessis, Cristina de Dios, Jose C Fernández-Checa, Montserrat Marí, Albert Morales, Tobias Hartmann, Anna Colell
Macroautophagy/autophagy failure with the accumulation of autophagosomes is an early neuropathological feature of Alzheimer disease (AD) that directly affects amyloid beta (Aβ) metabolism. Although loss of presenilin 1 function has been reported to impair lysosomal function and prevent autophagy flux, the detailed mechanism leading to autophagy dysfunction in AD remains to be elucidated. The resemblance between pathological hallmarks of AD and Niemann-Pick Type C disease, including endosome-lysosome abnormalities and impaired autophagy, suggests cholesterol accumulation as a common link...
June 4, 2018: Autophagy
https://www.readbyqxmd.com/read/29852178/ezetimibe-a-npc1l1-inhibitor-attenuates-neuronal-apoptosis-through-ampk-dependent-autophagy-activation-after-mcao-in-rats
#12
Jing Yu, Xue Li, Nathanael Matei, Devin McBride, Jiping Tang, Min Yan, John H Zhang
Autophagy activation exerts neuroprotective effects in the ischemic stroke model. Ezetimibe (Eze), a Niemann-Pick disease type C1-Like 1 (NPC1L1) pharmacological inhibitor, has been reported to protect hepatocytes from apoptosis via autophagy activation. In this study, we explored whether Eze could attenuate neuronal apoptosis in the rat model of middle cerebral artery occlusion (MCAO), specifically via activation of the AMPK/ULK1/autophagy pathway. Two hundred and one male Sprague-Dawley rats were subjected to transient MCAO followed by reperfusion...
May 28, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29845436/macula-halo-syndrome
#13
İsmail Umut Onur, Memhet Fatih Aşula, Cansu Ekinci, Meral Mert
INTRODUCTION: Niemann-Pick disease (NPD) is a hereditary lysosomal storage disorder in which mutations in the sphingomyelin phosphodiesterase gene leads to partial or complete deficiency of the sphingomyelinase enzyme. Niemann-Pick Type B is the intermediate form associated with hepatosplenomegaly, foam cells in the bone marrow, hyperlipidemia and diffuse pulmonary infiltrates, which is generally diagnosed in late adolescence. Central nervous system is not affected, and some cases may display macular halo...
May 29, 2018: International Ophthalmology
https://www.readbyqxmd.com/read/29783784/cyclodextrins-assessing-the-impact-of-cavity-size-occupancy-and-substitutions-on-cytotoxicity-and-cholesterol-homeostasis
#14
Lajos Szente, Ashutosh Singhal, Andras Domokos, Byeongwoon Song
Cyclodextrins (CDs) are cyclic oligosaccharides; the most common CDs contain six, seven, or eight glucose units called α-CDs, β-CDs, and γ-CDs, respectively. The use of CDs in biomedical research is increasing due to their ability to interact with membrane lipids as well as a wide variety of poorly water-soluble molecules. We assessed the impact of CD cavity size, occupancy, and substitutions on cytotoxicity and cholesterol homeostasis. The potency of CD-mediated cytotoxicity was in the order of β-CDs, α-CDs, and γ-CDs...
May 20, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29764733/genetic-polymorphism-of-sterol-transporters-in-children-with-future-gallstones
#15
Markku J Nissinen, Niina Pitkänen, Piia Simonen, Helena Gylling, Jorma Viikari, Olli Raitakari, Terho Lehtimäki, Markus Juonala, Mikko P Pakarinen
BACKGROUND & AIMS: Gallstone disease is related to hypersecretion of cholesterol in bile, and low serum phytosterol levels. We examined how genetic polymorphisms of sterol transporters affect childhood cholesterol metabolism trait predicting adult gallstone disease. PATIENTS AND METHODS: In retrospective controlled study, we determined D19H polymorphism of ABCG8 gene, genetic variation at Niemann-Pick C1-like 1 (NPC1L1) gene locus (rs41279633, rs17655652, rs2072183, rs217434 and rs2073548), and serum cholesterol, noncholesterol sterols and lipids in children affected by gallstones decades later (n = 66) and controls (n = 126)...
April 26, 2018: Digestive and Liver Disease
https://www.readbyqxmd.com/read/29759592/ccdc115-cdg-a-new-rare-and-misleading-inherited-cause-of-liver-disease
#16
Muriel Girard, Aurélia Poujois, Monique Fabre, Florence Lacaille, Dominique Debray, Marlène Rio, François Fenaille, Sophie Cholet, Coralie Ruel, Elizabeth Caussé, Janick Selves, Laure Bridoux-Henno, France Woimant, Thierry Dupré, Sandrine Vuillaumier-Barrot, Nathalie Seta, Laurent Alric, Pascale de Lonlay, Arnaud Bruneel
Congenital disorders of glycosylation (CDG) linked to defects in Golgi apparatus homeostasis constitute an increasing part of these rare inherited diseases. Among them, COG-CDG, ATP6V0A2-CDG, TMEM199-CDG and CCDC115-CDG have been shown to disturb Golgi vesicular trafficking and/or lumen pH acidification. Here, we report 3 new unrelated cases of CCDC115-CDG with emphasis on diagnosis difficulties related to strong phenotypic similarities with mitochondriopathies, Niemann-Pick disease C and Wilson Disease. Indeed, while two individuals clinically presented with early and severe liver fibrosis and cirrhosis associated with neurological symptoms, the other one "only" showed isolated and late severe liver involvement...
May 9, 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29753706/improvement-of-impaired-electrical-activity-in-npc1-mutant-cortical-neurons-upon-dhpg-stimulation-detected-by-micro-electrode-array
#17
Xiao Feng, Benjamin M Bader, Fan Yang, Monica Segura, Luise Schultz, Olaf H-U Schröder, Arndt Rolfs, Jiankai Luo
Niemann-Pick Type C1 (NPC1) disease is an autosomal recessive neurodegenerative disease characterized by an excessive accumulation of unesterified cholesterol in late endosomes/lysosomes. Patients with NPC1 disease show a series of symptoms in neuropathology, including a gradually increased loss of motor control and seizures. However, mechanism of the neurological manifestations in NPC1 disease is not fully understood yet. In this study, we utilized the micro-electrode array (MEA) to analyze the spontaneous extracellular electrical activity in cultivated cortical neurons of the NPC1 mutant (NPC1-/- ) mouse...
May 10, 2018: Brain Research
https://www.readbyqxmd.com/read/29725814/inhibition-of-mir-486-and-mir-92a-decreases-liver-and-plasma-cholesterol-levels-by-modulating-lipid-related-genes-in-hyperlipidemic-hamsters
#18
Loredan S Niculescu, Natalia Simionescu, Elena V Fuior, Camelia S Stancu, Mihaela G Carnuta, Madalina D Dulceanu, Mina Raileanu, Emanuel Dragan, Anca V Sima
In the present study we aimed to evaluate the potential of in vivo inhibition of miR-486 and miR-92a to reverse hyperlipidemia, then to identify and validate their lipid metabolism-related target genes. Male Golden-Syrian hamsters fed a hyperlipidemic (HL) diet (standard chow plus 3% cholesterol and 15% butter, 10 weeks) were injected subcutaneously with lock-nucleic acid inhibitors for either miR-486 or miR-92a. Lipids and miRNAs levels in liver and plasma, and hepatic expression of miRNAs target genes were assessed in all HL hamsters...
May 3, 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/29721961/early-endosome-morphology-in-health-and-disease
#19
Gulpreet Kaur, Aparna Lakkaraju
Early endosomes are organelles that receive macromolecules and solutes from the extracellular environment. The major function of early endosomes is to sort these cargos into recycling and degradative compartments of the cell. Degradation of the cargo involves maturation of early endosomes into late endosomes, which, after acquisition of hydrolytic enzymes, form lysosomes. Endosome maturation involves recruitment of specific proteins and lipids to the early endosomal membrane, which drives changes in endosome morphology...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29718288/the-pathogenesis-of-lysosomal-storage-disorders-beyond-the-engorgement-of-lysosomes-to-abnormal-development-and-neuroinflammation
#20
Maria Teresa Fiorenza, Enrico Moro, Robert P Erickson
There is growing evidence that the complex clinical manifestations of lysosomal storage diseases (LSDs) are not fully explained by the engorgement of the endosomal-autophagic-lysosomal system. In this review, we explore current knowledge of common pathogenetic mechanisms responsible for the early onset of tissue abnormalities of two LSDs, Mucopolysaccharidosis type II (MPSII) and Niemann-Pick type C (NPC) diseases. In particular, perturbations of the homeostasis of glycosaminoglycans (GAGs) and cholesterol (Chol) in MPSII and NPC diseases, respectively, affect key biological processes, including morphogen signaling...
April 28, 2018: Human Molecular Genetics
keyword
keyword
90270
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"