Neurobiology of Disease A Murine Niemann-Pick C1 I1061T Knock-In Model Recapitulates the Pathological Features of the Most Prevalent Human Disease Allele
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چکیده
Maria Praggastis,1 Brett Tortelli,1 Jessie Zhang,1 Hideji Fujiwara,1 Rohini Sidhu,1 Anita Chacko,1 Zhouji Chen,1 X Chan Chung,2 Andrew P. Lieberman,2 Jakub Sikora,3 Cristin Davidson,3 Steven U. Walkley,3 Nina H. Pipalia,4 Frederick R. Maxfield,4 Jean E. Schaffer,1 and Daniel S. Ory1 1Diabetic Cardiovascular Disease Center and Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, 2Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, 3Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Intellectual and Developmental Disabilities Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, and 4Department of Biochemistry, Weill Cornell Medical College, New York, New York 10065
منابع مشابه
A murine Niemann-Pick C1 I1061T knock-in model recapitulates the pathological features of the most prevalent human disease allele.
Niemann-Pick Type C1 (NPC1) disease is a rare neurovisceral, cholesterol-sphingolipid lysosomal storage disorder characterized by ataxia, motor impairment, progressive intellectual decline, and dementia. The most prevalent mutation, NPC1(I1061T), encodes a misfolded protein with a reduced half-life caused by ER-associated degradation. Therapies directed at stabilization of the mutant NPC1 prote...
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Niemann-Pick type C1 (NPC1) is a polytopic endosomal membrane protein required for efflux of LDL-derived cholesterol from endosomes, and mutations of this protein are associated with Niemann-Pick disease type C, a fatal neurodegenerative disease. At least one prevalent mutation (I1061T) has been shown to cause a folding defect, which results in failure of endosomal localization, leading to a lo...
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Niemann-Pick type C (NPC) disease is a fatal neurodegenerative disorder characterized by the accumulation of unesterified cholesterol in the late endosomal/lysosomal compartments. Mutations in the NPC1 protein are implicated in 95% of patients with NPC disease. The most prevalent mutation is the missense mutation I1061T that occurs in ∼ 15-20% of the disease alleles. In our study, an isobaric l...
متن کاملAberrant Promoter Methylation Profile of Niemann-Pick Type C1 Gene in Cardiovascular Disease
Background: The protein of Niemann-pick type C1 (NPC1) gene promotes the egress of cholesterol from late endosomes and lysosomes to other cellular compartments and contributes to a process known as reverse cholesterol transport. This study aimed to examine whether promoter methylation of NPC1 is associated with risk of cardiovascular disease (CVD). Methods: Fifty CVD patients and 50 healthy sub...
متن کاملRyanodine receptor antagonists adapt NPC1 proteostasis to ameliorate lipid storage in Niemann-Pick type C disease fibroblasts.
Niemann-Pick type C disease is a lysosomal storage disorder most often caused by loss-of-function mutations in the NPC1 gene. The encoded multipass transmembrane protein is required for cholesterol efflux from late endosomes and lysosomes. Numerous missense mutations in the NPC1 gene cause disease, including the prevalent I1061T mutation that leads to protein misfolding and degradation. Here, w...
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تاریخ انتشار 2015