anti-Niemann-Pick Disease, Type C1 (NPC1) Antikörper

Zebrafish Niemann-Pick Disease, Type C1 (NPC1) Interaktionspartner

1. this is the first report, showing a role of NPC1 in platelet function and formation but further studies are needed to define how cholesterol storage interferes with these processes

2. npc1 is required early for proper cell movement and cholesterol localization and later for cell survival

Rabbit Niemann-Pick Disease, Type C1 (NPC1) Interaktionspartner

1. Availability of assays to measure NPC1 binding to membrne proteins may further the understanding of ways in which oxysterols regulate intracellular lipid transport.

Mouse (Murine) Niemann-Pick Disease, Type C1 (NPC1) Interaktionspartner

1. Since we had previously shown the beneficial effects of probucol on the somatic phenotype in the Npc1(-/-) mice, we have now studied the effects of combined therapy with HPBCD and probucol on the lung with mostly negative results. Body weight and lung weight for body weight were increased in parallel while inspiratory capacity for body weight was markedly decreased.

2. We identified CD22 as a marker of dysregulated microglia in Npc1 mutant mice and subsequently demonstrated that elevated cerebrospinal fluid levels of CD22 in NPC1 patients responds to HPbetaCD administration. Collectively, these data provide the first in-depth analysis of microglia function in NPC1 and suggest possible new therapeutic approaches.

3. extracellular cholesterol concentration in serum under conditions of Npc1 deficiency can influence intracellular cholesterol content/distribution and lysosomal efficacy, triggering the accumulation of toxic APP-cleaved products, eventually leading to cell death.

4. Mutation in the NPC1 gene is associated with Niemann-Pick type C.

5. This study shown 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)

6. High-resolution respirometry analyses revealed that GSH-EE improved oxidative phosphorylation, coupled respiration and maximal electron transfer in cerebellum of Npc1(-/-) mice

7. Lysosomal oxLDL accumulation within macrophages contributes to murine atherosclerosis. Prevention of oxLDL uptake leads to decreased atherosclerosis in hematopoietic NPC1-deficient Ldlr(-/-) mice

8. the spleen is significantly enlarged in Npc1(-/-) mice.

9. Study is the first data to reveal motor and behavioral deficits in early maturity of Npc1+/- mice.

10. Npc1 gene interacts with a high fat diet to promote weight gain through differential regulation of central energy metabolism pathways.

11. AAV9-mediated NPC1 delivery significantly promoted Purkinje cell survival, restored locomotor activity and coordination, and increased the lifespan of NPC1(-/-) mice. Our work suggests that AAV-based gene therapy is a promising means to treat NPC disease.

12. Here, we identify lamellar inclusions as the subcellular site of lipid accumulation in neurons, we uncover a vicious cycle of cholesterol synthesis and accretion, which may cause gradual neurodegeneration, and we reveal how beta-cyclodextrin, a potential therapeutic drug, reverts these changes. Our study provides new mechanistic insight in NPC disease and uncovers new targets for therapeutic approaches.

13. Male NPC1+/- mice had increased fat storage while eating a high-fat diet.

14. Our data show that: i) HDAC2 levels and activity are increased in NPC neuronal models and in Npc1(-/-) mice; ii) inhibition of c-Abl or c-Abl deficiency prevents the increase of HDAC2 protein levels and activity in NPC neuronal models

15. activation of the alternative pathway is involved in Niemann-Pick C1 associated pulmonary macrophage accumulation, with low proliferation of these cells balanced by low levels of apoptosis.

16. This study showed that deleting the Npc1 gene is accompanied by an increase in germ cell apoptosis and compensatory imbalances in the expression of cholesterol enzymatic and transporter factors.

17. These results show that NPC1 is critical for ebolavirus replication and pathogenesis in animals.

18. abnormal neuronal expression of matrix metalloproteinase-12 may contribute to axonal degeneration in Niemann-Pick type C disease

19. There was a transient increase in biliary cholesterol concentration in Npc1(-/-) mice.

20. data suggest that aberrant expression of Pcdhs is a pathological process accompanied by neurodegeneration in Npc1 mutant mice

Human Niemann-Pick Disease, Type C1 (NPC1) Interaktionspartner

1. Human NPC1 SNPs may likely affect host susceptibility to filoviruses.

2. Niemann-Pick C1 protein (NPC1) gene expression showed positive significant correlation with interleukin 10 (IL-10) serum concentration.

3. In contrast to the benign Q92S mutation, Q92R significantly reduces electrostatic potential around S-opening, and thus likely affects NPC1 (NTD)-NPC2 interaction and/or cholesterol transfer from NPC2 to NPC1.

4. Mutation in the NPC1 gene is associated with Niemann-Pick type C1 disease.

5. We identified CD22 as a marker of dysregulated microglia in Npc1 mutant mice and subsequently demonstrated that elevated cerebrospinal fluid levels of CD22 in NPC1 patients responds to HPbetaCD administration. Collectively, these data provide the first in-depth analysis of microglia function in NPC1 and suggest possible new therapeutic approaches.

6. these findings confirm the utility of high-content image-based compound screens of NPC1 patient cells and support extending the approach into larger compound collections.

7. We also identified LNA ASOs targeting human host factor NPC1 and demonstrated reduced infection by chimeric vesicular stomatitis virus harboring the Ebola glycoprotein, which directly binds to NPC1 for viral infection.

8. mutant NPC1 degradation is regulated by selective endoplasmic reticulum autophagy and MARCH6-dependent endoplasmic-reticulum-associated degradation

9. NPC1 gene variations may predispose to common metabolic diseases by modulating steroid hormone synthesis and/or lipid homeostasis.

10. Results propose that, depending on the location of the cholesterol ligand, a dynamical interface between the NPC2 and NPC1 N-terminal domain (NTD) proteins exists. Structural features of a particular interface can lower the energy barrier and stabilize the passage of the cholesterol substrate from NPC2 to NPC1(NTD).

11. These data support the hypothesis that cholesterol is transported through interactions between two or more NPC1 molecules.

12. Mutation in the NPC1 gene is associated with Niemann-Pick type C.

13. pronounced alterations in several proteins linked to autophagy and lysosomal catabolism reflecting vesicular transport obstruction and defective lysosomal turnover resulting from NPC1 deficiency, were observed.

14. Niemann-Pick C1 (NPC1) protein structures suggest mapping of all of the disease-causing mutations for future molecular insights into the pathogenesis of Niemann-Pick type C disease (NPC) disease.

15. This study demonistrated that heterozygous mutations of NPC1 genes could contribute to dementia plus, at least in a subset of patients.

16. Docking of the NPC1-NPC2 complex onto the full-length NPC1 structure reveals a direct cholesterol transfer tunnel between NPC2 and N-terminal domain cholesterol binding pockets, supporting the "hydrophobic hand-off" cholesterol transfer model.

17. Taken together, these studies suggest that Ebola virus requires phosphatidylinositol (3,5) bisphosphate production in cells to promote efficient delivery to NPC1.

18. identification of NPC1 and/or NPC2 mutations combined with descriptions of clinical phenotype, will improve our knowledge of pathogenic mutations and our understanding of genotype-phenotype correlations.

19. Here we report a crystal structure of a large fragment of human NPC1 at 3.6 A resolution, which reveals internal twofold pseudosymmetry along TM 2-13 and two structurally homologous domains that protrude 60 A into the endosomal lumen, and we propose a model for NPC1 function in cholesterol sensing and transport.

20. Sequencing of genomic DNA from GM03123 Led to the identification of a mutation in NPC1 GENE, g.41940G>C (c.1947 + 5G>C; rs770321568) (Fig. 1A), with a minor allele frequency of 0.0000082