نتایج جستجو برای: npc1

تعداد نتایج: 544  

2016
Meghann W Lau Ryan W Lee Robin Miyamoto Eun Sol Jung Nicole Yanjanin Farhat Shoko Yoshida Susumu Mori Andrea Gropman Eva H Baker Forbes D Porter

Niemann-Pick Disease, type C1 (NPC1) is a rapidly progressive neurodegenerative disorder characterized by cholesterol sequestration within late endosomes and lysosomes, for which no reliable imaging marker exists for prognostication and management. Cerebellar volume deficits are found to correlate with disease severity and diffusion tensor imaging (DTI) of the corpus callosum and brainstem, whi...

2009
Stefania Zampieri Synthia H Mellon Terry D Butters Marco Nevyjel Douglas F Covey Bruno Bembi Andrea Dardis

Niemann-Pick C disease (NPC) is an autosomal recessive neurodegenerative disorder caused by the abnormal function of NPC1 or NPC2 proteins, leading to an accumulation of unesterified cholesterol and glycosphingolipids (GSLs) in the lysosomes. The mechanisms underlying the pathophysiology in NPC disease are not clear. Oxidative damage is implicated in the pathophysiology of different neurologica...

2012
Zachary T. Wehrmann Tyler W. Hulett Kara L. Huegel Kevin T. Vaughan Olaf Wiest Paul Helquist Holly Goodson

Niemann-Pick Type C disease (NPC) is a lethal, autosomal recessive disorder caused by mutations in the NPC1 and NPC2 cholesterol transport proteins. NPC's hallmark symptoms include an accumulation of unesterified cholesterol and other lipids in the late endosomal and lysosomal cellular compartments, causing progressive neurodegeneration and death. Although the age of onset may vary in those aff...

Journal: :PLoS ONE 2006
Jonathan V. Reddy Ian G. Ganley Suzanne R. Pfeffer

BACKGROUND Niemann-Pick Type C (NPC) disease is a neurodegenerative disease that is characterized by the accumulation of cholesterol and glycosphingolipids in the late endocytic pathway. The majority of NPC cases are due to mutations in the NPC1 gene. The precise function of this gene is not yet known. METHODOLOGY/PRINCIPAL FINDINGS Using cDNA microarrays, we analyzed the genome-wide expressi...

2010
Qingyu Qin Guanghong Liao Michel Baudry Xiaoning Bi

Perturbation of lipid metabolism, especially of cholesterol homeostasis, can be catastrophic to mammalian brain, as it has the highest level of cholesterol in the body. This notion is best illustrated by the severe progressive neurodegeneration in Niemann-Pick Type C (NPC) disease, one of the lysosomal storage diseases, caused by mutations in the NPC1 or NPC2 gene. In this study, we found that ...

Journal: :The Journal of clinical investigation 2014
Danielle te Vruchte Anneliese O Speak Kerri L Wallom Nada Al Eisa David A Smith Christian J Hendriksz Louise Simmons Robin H Lachmann Alison Cousins Ralf Hartung Eugen Mengel Heiko Runz Michael Beck Yasmina Amraoui Jackie Imrie Elizabeth Jacklin Kate Riddick Nicole M Yanjanin Christopher A Wassif Arndt Rolfs Florian Rimmele Naomi Wright Clare Taylor Uma Ramaswami Timothy M Cox Caroline Hastings Xuntian Jiang Rohini Sidhu Daniel S Ory Begona Arias Mylvaganam Jeyakumar Daniel J Sillence James E Wraith Forbes D Porter Mario Cortina-Borja Frances M Platt

Lysosomal storage disorders (LSDs) occur at a frequency of 1 in every 5,000 live births and are a common cause of pediatric neurodegenerative disease. The relatively small number of patients with LSDs and lack of validated biomarkers are substantial challenges for clinical trial design. Here, we evaluated the use of a commercially available fluorescent probe, Lysotracker, that can be used to me...

2009
Yu Sun Minako Ishibashi Tracie Seimon Mingsum Lee Sudarshana M. Sharma Katherine A. Fitzgerald Andriy O. Samokhin Yibin Wang Scott Sayers Masanori Aikawa W. Gray Jerome Michael C. Ostrowski Dieter Bromme Peter Libby Ira A. Tabas Carrie L. Welch Alan R. Tall

The molecular events linking lipid accumulation in atherosclerotic plaques to complications such as aneurysm formation and plaque disruption are poorly understood. BALB/c-Apoe / mice bearing a null mutation in the Npc1 gene display prominent medial erosion and atherothrombosis, whereas their macrophages accumulate free cholesterol in late endosomes and show increased cathepsin K (Ctsk) expressi...

2017
Sheng Dai Andrés E Dulcey Xin Hu Christopher A Wassif Forbes D Porter Christopher P Austin Daniel S Ory Juan Marugan Wei Zheng

The drug 2-hydroxypropyl-β-cyclodextrin (HPβCD) reduces lysosomal cholesterol accumulation in Niemann-Pick disease, type C (NPC) and has been advanced to human clinical trials. However, its mechanism of action for reducing cholesterol accumulation in NPC cells is uncertain and its molecular target is unknown. We found that methyl-β-cyclodextrin (MβCD), a potent analog of HPβCD, restored impaire...

Journal: :Circulation research 2009
Yu Sun Minako Ishibashi Tracie Seimon Mingsum Lee Sudarshana M Sharma Katherine A Fitzgerald Andriy O Samokhin Yibin Wang Scott Sayers Masanori Aikawa W Gray Jerome Michael C Ostrowski Dieter Bromme Peter Libby Ira A Tabas Carrie L Welch Alan R Tall

The molecular events linking lipid accumulation in atherosclerotic plaques to complications such as aneurysm formation and plaque disruption are poorly understood. BALB/c-Apoe(-/-) mice bearing a null mutation in the Npc1 gene display prominent medial erosion and atherothrombosis, whereas their macrophages accumulate free cholesterol in late endosomes and show increased cathepsin K (Ctsk) expre...

Journal: :Cell 2016
William E. Diehl Aaron E. Lin Nathan D. Grubaugh Luiz Max Carvalho Kyusik Kim Pyae Phyo Kyawe Sean M. McCauley Elisa Donnard Alper Kucukural Patrick McDonel Stephen F. Schaffner Manuel Garber Andrew Rambaut Kristian G. Andersen Pardis C. Sabeti Jeremy Luban

The magnitude of the 2013-2016 Ebola virus disease (EVD) epidemic enabled an unprecedented number of viral mutations to occur over successive human-to-human transmission events, increasing the probability that adaptation to the human host occurred during the outbreak. We investigated one nonsynonymous mutation, Ebola virus (EBOV) glycoprotein (GP) mutant A82V, for its effect on viral infectivit...

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