Read by QxMD icon Read

niemann-pick type c

Takeshi Funakoshi, Toshihiko Aki, Masateru Tajiri, Kana Unuma, Koichi Uemura
Aberrant cellular accumulation of cholesterol is associated with neuronal lysosomal storage disorders such as Niemann-Pick disease Type C (NPC). We have shown previously that l-norephedrine (l-Nor), a sympathomimetic amine, induces necrotic cell death associated with massive cytoplasmic vacuolation in SH-SY5Y human neuroblastoma cells. To reveal the molecular mechanism underling necrotic neuronal cell death caused by l-Nor, we examined alterations in the gene expression profile of cells during l-Nor exposure...
October 18, 2016: Journal of Biological Chemistry
Yuki Kondo, Hiroko Tokumaru, Yoichi Ishitsuka, Tomoko Matsumoto, Makiko Taguchi, Keiichi Motoyama, Taishi Higashi, Hidetoshi Arima, Muneaki Matsuo, Katsumi Higaki, Kousaku Ohno, Tetsumi Irie
No abstract text is available yet for this article.
October 9, 2016: Molecular Genetics and Metabolism
Yan-Feng Zhou, Matthew C Metcalf, Scott C Garman, Tim Edmunds, Huawei Qiu, Ronnie R Wei
Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann-Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site...
October 11, 2016: Nature Communications
Yoojin Seo, Hyung-Sik Kim, Insung Kang, Soon Won Choi, Tae-Hoon Shin, Ji-Hee Shin, Byung-Chul Lee, Jin Young Lee, Jae-Jun Kim, Myung Geun Kook, Kyung-Sun Kang
Microglia can aggravate olfactory dysfunction by mediating neuronal death in the olfactory bulb (OB) of a murine model of Niemann-Pick disease type C1 (NPC1), a fatal neurodegenerative disorder accompanied by lipid trafficking defects. In this study, we focused on the crosstalk between neurons and microglia to elucidate the mechanisms underlying extensive microgliosis in the NPC1-affected brain. Microglia in the OB of NPC1 mice strongly expressed CX3C chemokine receptor 1 (Cx3cr1), a specific receptor for the neural chemokine C-X3-C motif ligand 1 (Cx3cl1)...
September 30, 2016: Glia
Eva-Maria Kuech, Graham Brogden, Hassan Y Naim
Lysosomal storage disorders are a heterogeneous group of more than 50 distinct inborn metabolic diseases affecting about 1 in 5000 to 7000 live births. The diseases often result from mutations followed by functional deficiencies of enzymes or transporters within the acidic environment of the lysosome, which mediate the degradation of a wide subset of substrates, including glycosphingolipids, glycosaminoglycans, cholesterol, glycogen, oligosaccharides, peptides and glycoproteins, or the export of the respective degradation products from the lysosomes...
September 21, 2016: Biochimie
Haitang Wang, Yuen Yi C Tam, Sam Chen, Josh Zaifman, Roy van der Meel, Marco A Ciufolini, Pieter R Cullis
The therapeutic applications of lipid nanoparticle (LNP) formulations of small interfering RNA (siRNA) are hampered by inefficient delivery of encapsulated siRNA to the cytoplasm following endocytosis. Recent work has shown that up to 70% of endocytosed LNP-siRNA particles are recycled to the extracellular medium and thus cannot contribute to gene silencing. Niemann-Pick type C1 (NPC1) is a late endosomal/lysosomal membrane protein required for efficient extracellular recycling of endosomal contents. Here we assess the influence of NP3...
September 16, 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
A Pérez-Cañamás, S Benvegnù, C B Rueda, A Rábano, J Satrústegui, M D Ledesma
Niemann-Pick disease type A (NPA) is a rare lysosomal storage disorder characterized by severe neurological alterations that leads to death in childhood. Loss-of-function mutations in the acid sphingomyelinase (ASM) gene cause NPA, and result in the accumulation of sphingomyelin (SM) in lysosomes and plasma membrane of neurons. Using ASM knockout (ASMko) mice as a NPA disease model, we investigated how high SM levels contribute to neural pathology in NPA. We found high levels of oxidative stress both in neurons from these mice and a NPA patient...
September 13, 2016: Molecular Psychiatry
Thomas Kirkegaard, James Gray, David A Priestman, Kerri-Lee Wallom, Jennifer Atkins, Ole Dines Olsen, Alexander Klein, Svetlana Drndarski, Nikolaj H T Petersen, Linda Ingemann, David A Smith, Lauren Morris, Claus Bornæs, Signe Humle Jørgensen, Ian Williams, Anders Hinsby, Christoph Arenz, David Begley, Marja Jäättelä, Frances M Platt
Lysosomal storage diseases (LSDs) often manifest with severe systemic and central nervous system (CNS) symptoms. The existing treatment options are limited and have no or only modest efficacy against neurological manifestations of disease. We demonstrate that recombinant human heat shock protein 70 (HSP70) improves the binding of several sphingolipid-degrading enzymes to their essential cofactor bis(monoacyl)glycerophosphate in vitro. HSP70 treatment reversed lysosomal pathology in primary fibroblasts from 14 patients with eight different LSDs...
September 7, 2016: Science Translational Medicine
Keiichi Motoyama, Rena Nishiyama, Yuki Maeda, Taishi Higashi, Yoshimasa Kawaguchi, Shiroh Futaki, Yoichi Ishitsuka, Yuki Kondo, Tetsumi Irie, Takumi Era, Hidetoshi Arima
Niemann-Pick disease type C (NPC) is an autosomal recessive lysosomal storage disorder, which is an inherited disease characterized by the accumulation of unesterified cholesterol in endolysosomes. Recently, 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) has been used for the treatment of NPC, and ameliorated a hepatosplenomegaly in the patients. However, to obtain the treatment efficacy, a high dose of HP-β-CyD was necessary. Therefore, the decrease in dose by using active intracellular delivery system of β-CyD to NPC cells is expected...
September 6, 2016: Biological & Pharmaceutical Bulletin
Jean-Marie Cuisset, S Sukno, A Trauffler, P Latour, D Dobbelaere, L Michaud, L Vallée
BACKGROUND: Niemann-Pick disease type C is a rare inherited neurodegenerative disease involving impaired intracellular lipid trafficking and accumulation of glycolipids in various tissues, including the brain. Miglustat, a reversible inhibitor of glucosylceramide synthase, has been shown to be effective in the treatment of progressive neurological manifestations in pediatric and adult patients with Niemann-Pick disease type C, and has been used in that indication in Europe since 2010...
2016: Journal of Medical Case Reports
L H Koens, A Kuiper, M A Coenen, J W J Elting, J J de Vries, M Engelen, J H T M Koelman, F J van Spronsen, J M Spikman, T J de Koning, M A J Tijssen
BACKGROUND: Niemann-Pick type C (NP-C) is a rare autosomal recessive progressive neurodegenerative disorder caused by mutations in the NP-C 1 or 2 gene. Besides visceral symptoms, presentation in adolescent and adult onset variants is often with neurological symptoms. The most frequently reported presenting symptoms of NP-C in adulthood are psychiatric symptoms (38 %), cognitive decline (23 %) and ataxia (20 %). Myoclonus can be present, but its value in early diagnosis and the evolving clinical phenotype in NP-C is unclear...
September 1, 2016: Orphanet Journal of Rare Diseases
Anna Brown, Siddharth Patel, Carl Ward, Anna Lorenz, Mauren Ortiz, Allison DuRoss, Fabian Wieghardt, Amanda Esch, Elsje G Otten, Laura M Heiser, Viktor I Korolchuk, Conroy Sun, Sovan Sarkar, Gaurav Sahay
2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1(-/-)) cells...
2016: Scientific Reports
M J Yáñez, O Belbin, L D Estrada, N Leal, P S Contreras, A Lleó, P V Burgos, S Zanlungo, A R Alvarez
BACKGROUND: Niemann-Pick type C (NPC) disease is characterized by lysosomal accumulation of cholesterol. Interestingly, NPC patients' brains also show increased levels of amyloid-β (Aβ) peptide, a key protein in Alzheimer's disease pathogenesis. We previously reported that the c-Abl tyrosine kinase is active in NPC neurons and in AD animal models and that Imatinib, a specific c-Abl inhibitor, decreased the amyloid burden in brains of the AD mouse model. Active c-Abl was shown to interact with the APP cytosolic domain, but the relevance of this interaction to APP processing has yet to be defined...
August 23, 2016: Biochimica et Biophysica Acta
Xiaochun Li, Piyali Saha, Jian Li, Günter Blobel, Suzanne R Pfeffer
Export of LDL-derived cholesterol from lysosomes requires the cooperation of the integral membrane protein Niemann-Pick C1 (NPC1) and a soluble protein, Niemann-Pick C2 (NPC2). Mutations in the genes encoding these proteins lead to Niemann-Pick disease type C (NPC). NPC2 binds to NPC1's second (middle), lumenally oriented domain (MLD) and transfers cholesterol to NPC1's N-terminal domain (NTD). Here, we report the 2.4-Å resolution crystal structure of a complex of human NPC1-MLD and NPC2 bearing bound cholesterol-3-O-sulfate...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
Niraj Kumar, Philippe Rizek, Yahia Mohammad, Mandar Jog
No abstract text is available yet for this article.
August 23, 2016: Neurology
Marivi Cervera-Gaviria, Miguel Angel Alcántara-Ortigoza, Ariadna González-Del Angel, Paola Moyers-Pérez, Blanca Gabriela Lizet Legorreta-Ramírez, Nancy Barrera-Carmona, Jaime Cervera-Gaviria
BACKGROUND: Niemann-Pick disease type C (NP-C) is a fatal lysosomal neurodegenerative and neurovisceral disease. It is caused by defects in intracellular lipid trafficking, which lead to the accumulation of lipids and glycosphingolipids within the endosomes and lysosomes of affected individuals. Pathogenic variants of the NPC1 or NPC2 genes yield highly variable phenotypes with a time course that ranges from fetal onset (i.e., hydrops fetalis) to progressive dementia in adults. NP-C is typically inherited in an autosomal-recessive manner...
2016: BMC Neurology
Tatiana Bremova, Siegbert Krafczyk, Stanislavs Bardins, Jörg Reinke, Michael Strupp
We investigated whether vestibular dysfunction may cause or contribute to postural imbalance and falls in patients with Niemann-Pick type C disease (NP-C). Eight patients with NP-C disease and 20 healthy controls were examined using the video-based head impulse test (vHIT) and caloric irrigation to investigate horizontal canal function as well as ocular- and cervical vestibular evoked myogenic potentials (o- and cVEMP), and binocular subjective visual vertical estimation (SVV) for otolith function, and static posturography...
November 2016: Journal of Neurology
Naohiro Hashimoto, Ikiru Matsumoto, Hiromasa Takahashi, Hitomi Ashikawa, Hiroyuki Nakamura, Toshihiko Murayama
Sphingolipids such as sphingomyelin and glycosphingolipids (GSLs) derived from glucosylceramide (GlcCer), in addition to cholesterol, accumulate in cells/neurons in Niemann-Pick disease type C (NPC). The activities of acid sphingomyelinase and lysosomal glucocerebrosidase (GCase), which degrade sphingomyelin and GlcCer, respectively, are down-regulated in NPC cells, however, changes in GlcCer synthase activity have not yet been elucidated. We herein demonstrated for the first time that GlcCer synthase activity for the fluorescent ceramide, 4-nitrobenzo-2-oxa-1,3-diazole-labeled C6-ceramide (NBD-ceramide) increased in intact NPC1((-/-)) cells and cell lysates without affecting the protein levels...
November 2016: Neuropharmacology
Giulia Polo, Alessandro P Burlina, Thilini B Kolamunnage, Michele Zampieri, Carlo Dionisi-Vici, Pietro Strisciuglio, Martina Zaninotto, Mario Plebani, Alberto B Burlina
BACKGROUND: Lysosphingolipids (LysoSLs) are derivatives of sphingolipids which have lost the amide-linked acyl chain. More recently, LysoSLs have been identified as storage compounds in several sphingolipidoses, including Gaucher, Fabry and Niemann-Pick diseases. To date, different methods have been developed to measure each individual lysosphingolipid in plasma. This report describes a rapid liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) assay for simultaneous quantification of several LysoSLs in plasma...
August 17, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
Asami Makino, Mitsuhiro Abe, Reiko Ishitsuka, Motohide Murate, Takuma Kishimoto, Shota Sakai, Françoise Hullin-Matsuda, Yukiko Shimada, Takehiko Inaba, Hideyuki Miyatake, Hideko Tanaka, Atsushi Kurahashi, Chan-Gi Pack, Rinshi S Kasai, Shuku Kubo, Nicole L Schieber, Naoshi Dohmae, Naoya Tochio, Kyoji Hagiwara, Yutaka Sasaki, Yoko Aida, Fumihiro Fujimori, Takanori Kigawa, Kozo Nishibori, Robert G Parton, Akihiro Kusumi, Yasushi Sako, Gregor Anderluh, Makoto Yamashita, Tetsuyuki Kobayashi, Peter Greimel, Toshihide Kobayashi
We identified a novel, nontoxic mushroom protein that specifically binds to a complex of sphingomyelin (SM), a major sphingolipid in mammalian cells, and cholesterol (Chol). The purified protein, termed Nakanori, labeled cell surface domains in an SM- and Chol-dependent manner and decorated specific lipid domains that colocalized with inner leaflet small GTPase H-Ras, but not K-Ras. The use of Nakanori as a lipid-domain-specific probe revealed altered distribution and dynamics of SM/Chol on the cell surface of Niemann-Pick type C fibroblasts, possibly explaining some of the disease phenotype...
August 4, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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"