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- Table of Contents
Facts about NPC intracellular cholesterol transporter 1.
Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket (PubMed:19563754). Binds oxysterol with greater affinity than cholesterol.
Human | |
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Gene Name: | NPC1 |
Uniprot: | O15118 |
Entrez: | 4864 |
Belongs to: |
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patched family |
FLJ98532; Niemann-Pick C1 protein; Niemann-Pick disease, type C1; Niemann-Pick Type C1; NPC; NPC1; SLC65A1
Mass (kDA):
142.167 kDA
Human | |
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Location: | 18q11.2 |
Sequence: | 18; NC_000018.10 (23506184..23586506, complement) |
Late endosome membrane; Multi-pass membrane protein. Lysosome membrane; Multi-pass membrane protein.
One of biology's most well-studied proteins is the NPC1 protein. Scientists have been trying to identify this protein for decades. However, it is not yet known what the best uses are. Steven Boster, a biomedical researcher, developed the NPC1 marker back in 1993. Boster's research led to the creation primary antibodies, iPSCs, as well as iPSDs.
The anti-NPC1 antibody won't cross react with NPC2, which is a gene that causes Niemann Pick type C disease. The antibody will react with NPC1 either in vitro or in vivo. This article describes the process of detecting the NPC1 antisenseRNA. The antibodies used are rabbit polyclonal antibody raised against the NPC1 human peptide. Secondary antibodies were Alexa Fluor 488, 555.
In a single blot, the antibody recognizes heterogeneously glycosylated NPC1 proteins. It identifies bands with molecular masses of approximately 170 and 220 kDa. The results obtained using mouse are mixed. However, the antibody has been tested in immuno-EM on human proteins. The antibody can be used for immuno-EM and electron microscopy as well as immunocytochemistry, immunofluorescence and immunoprecipitation.
The NPC1 protein has been shown to partially colocalize in synaptophysin. In a study, anti-synaptophysin antibodies were used to immunoprecipitate cerebellum homogenate. The antibodies bound synaptic vessels beads. The results showed that synaptophysin and NPC1 are colocalized within the neuronal vesicles.
His research on NPC1 has shown that microglia have this cell-autonomous protein. Chronic inflammation may result in the loss of NPC1. His research on NPC1 should not be considered an innocuous bystander to the development of neurodegeneration. His future plans include the development of therapies to target microglia. While more research is needed, it is clear that this protein has an important role in regulating neurodegeneration.
NPC1 genes are expressed in most brain cells and a large number of neurons. NPC1 levels are high in microglias and oligodendrocytes. NPC1 plays a crucial role in the maturation of OPCs as well as the maintenance of myelin. NPC1 is a gene that is found all over the brain. It is involved with the maturation of glia and their function.
His iPSC-derived neurons showed a punctate pattern, with bright staining in the cell body extensions and perinuclear regions, compared to a control, which had low overall fluorescence but no fluorescent vesicles. Similarly, the LSO compartment ratio of mutant cells showed elevated cholesterol. This result has implications for understanding the molecular mechanisms of NPC1 defects in human neuronal cells bearing different NPC1 mutations.
The study also identified ten potential pharmacological chaperones through molecular docking. The compounds were then tested in patient-specific fibroblasts carrying mutations in the NPC1 gene and in disease-affected cell types. This is the first study that has identified compounds that could be used as pharmacological chaperones. These findings are important for the future development of cell therapy for a wide array of conditions, including for cancer.
Vimentin levels and GFAP were significantly higher among NPC1 mutant fibroblasts. His-iPSC-derived cells for glial development had similar IF architecture. In immunocytochemical staining of vimentin, NPC1 mutant cells showed longer crisscrossed bundles. Similar changes were also observed in GFAP. These changes indicate a modified IF assembly.
The NPC1 gene encodes the protein that binds cholesterol. The mutations in NPC1 (or NPC2), which encode intracellular cholesterol binding proteins in the Lysosome, are responsible for the disease. Deficiency in either or both of these proteins can impair intracellular cholesterol transportation. This NPC1 iPSC ligand is a valuable resource to drug development and disease modeling.
The study also looked at the effect of NPC1 marker on GABAergic IPSC frequency. Although pathogenic mechanisms for NPC1-deficient mice remain largely elusive, accumulating data suggest that alteration in excitatory synaptic transmission in the neurons leads to altered inhibitory input to PCs. GABAergicIPSCs are also more common, as evidenced by NMDA/AMPA-Rs in inhibitory postsynaptic internurons.
Prof. Andreas Maetzel is a physician, health economist, clinical epidemiologist, and adjunct professor at the University of Zurich. His core expertise is health economic analyses. He has published more than 48 articles and served as chair of the Hamburg Secession. He has a background in clinical epidemiology, Bayesian modelling, and commercial forecasting & planning. His research on obesity and cardiovascular disease have influenced the development worldwide of health policies.
PMID: 9211849 by Carstea E.D., et al. Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis.
PMID: 10425213 by Morris J.A., et al. The genomic organization and polymorphism analysis of the human Niemann-Pick C1 gene.