NPC1L1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | NPC1L1 , NPC11L1, NPC1 like intracellular cholesterol transporter 1, SLC65A2, LDLCQ7 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 608010 MGI: 2685089 HomoloGene: 56585 GeneCards: NPC1L1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Niemann-Pick C1-Like 1 (NPC1L1) is a protein found on the gastrointestinal tract epithelial cells [5] as well as in hepatocytes. [6] Specifically, it appears to bind to a critical mediator of cholesterol absorption.
The drug ezetimibe inhibits NPC1L1 causing a reduction in cholesterol absorption, resulting in a blood cholesterol reduction of between 15-20%. [7] Polymorphic variations in NPC1L1 gene could be associated with non-response to ezetimibe treatment. [8]
NPC1L1 has been shown to be an accessory receptor for hepatitis C virus entry into cells, and thus ezetimibe might be used as a therapeutic strategy. [9]
As cancer appeared more frequently in patients treated with simvastatin-ezetimibe combination therapy in one clinical trial, [10] it had been hypothesized that NPC1L1 by ezetimibe might be associated with an increase cancer risk. [11] However a meta-analysis of ezetimibe clinical data showed no increased risk of cancer from treatment with ezetimibe. [12]
Statins are the most common cholesterol-lowering drugs. Also known as HMG-CoA reductase inhibitors, they are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease.
Lipid-lowering agents, also sometimes referred to as hypolipidemic agents, cholesterol-lowering drugs, or antihyperlipidemic agents are a diverse group of pharmaceuticals that are used to lower the level of lipids and lipoproteins such as cholesterol, in the blood (hyperlipidemia). The American Heart Association recommends the descriptor 'lipid lowering agent' be used for this class of drugs rather than the term 'hypolipidemic'.
Dyslipidemia is an abnormal amount of lipids in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). ASCVD includes coronary artery disease, cerebrovascular disease, and peripheral artery disease. Although dyslipidemia is a risk factor for ASCVD, abnormal levels don't mean that lipid lowering agents need to be started. Other factors, such as comorbid conditions and lifestyle in addition to dyslipidemia, is considered in a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin resistance can also lead to dyslipidemia. Likewise, increased levels of O-GlcNAc transferase (OGT) may cause dyslipidemia.
Niemann–Pick disease is a group of severe inherited metabolic disorders, in which sphingomyelin accumulates in lysosomes in cells.
Ezetimibe is a medication used to treat high blood cholesterol and certain other lipid abnormalities. Generally it is used together with dietary changes and a statin. Alone, it is less preferred than a statin. It is taken by mouth. It is also available in the fixed combinations ezetimibe/simvastatin, ezetimibe/atorvastatin, ezetimibe/rosuvastatin, and ezetimibe/bempedoic acid.
HMG-CoA reductase is the rate-controlling enzyme of the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids. HMGCR catalyzes the conversion of HMG-CoA to mevalonic acid, a necessary step in the biosynthesis of cholesterol. Normally in mammalian cells this enzyme is competitively suppressed so that its effect is controlled. This enzyme is the target of the widely available cholesterol-lowering drugs known collectively as the statins, which help treat dyslipidemia.
Ezetimibe/simvastatin is a drug combination used for the treatment of dyslipidemia. It is a combination of ezetimibe and the statin drug simvastatin.
In clinical trials, a surrogate endpoint is a measure of effect of a specific treatment that may correlate with a real clinical endpoint but does not necessarily have a guaranteed relationship. The National Institutes of Health (USA) defines surrogate endpoint as "a biomarker intended to substitute for a clinical endpoint".
Niemann-Pick disease, type C1 (NPC1) is a disease of a membrane protein that mediates intracellular cholesterol trafficking in mammals. In humans the protein is encoded by the NPC1 gene.
The epididymal secretory protein E1, also known as NPC2( Niemann-Pick intracellular cholesterol transporter 2), is one of two main lysosomal transport proteins that assist in the regulation of cellular cholesterol by exportation of LDL-derived cholesterol from lysosomes. Lysosomes have digestive enzymes that allow it to break down LDL particles to LDL-derived cholesterol once the LDL particle is engulfed into the cell via receptor mediated endocytosis.
Scavenger receptor class B type 1 (SRB1) also known as SR-BI is a protein that in humans is encoded by the SCARB1 gene. SR-BI functions as a receptor for high-density lipoprotein.
ATP-binding cassette sub-family G member 5 is a protein that in humans is encoded by the ABCG5 gene.
ATP-binding cassette sub-family G member 8 is a protein that in humans is encoded by the ABCG8 gene.
Contactin-associated protein-like 2 is a protein that in humans is encoded by the CNTNAP2 gene. Since the most recent reference human genome GRCh38, CNTNAP2 is the longest gene in the human genome
Sodium/bile acid cotransporter also known as the Na+-taurocholate cotransporting polypeptide (NTCP) or liver bile acid transporter (LBAT) is a protein that in humans is encoded by the SLC10A1 (solute carrier family 10 member 1) gene.
Niemann–Pick type C (NPC) is a lysosomal storage disease associated with mutations in NPC1 and NPC2 genes. Niemann–Pick type C affects an estimated 1:150,000 people. Approximately 50% of cases present before 10 years of age, but manifestations may first be recognized as late as the sixth decade.
Myelin regulatory factor, also known as myelin gene regulatory factor (MRF), is a protein that in humans is encoded by the MYRF gene.
A sterol-sensing domain (SSD) is a protein domain which consists of 180 amino acids forming five transmembrane segments capable of binding sterol groups. This type of domain is present in proteins involved in cholesterol metabolism and signalling.
Bempedoic acid, sold under the brand name Nexletol among others, is a medication for the treatment of hypercholesterolemia.
Bempedoic acid/ezetimibe, sold under the brand name Nexlizet among others, is a fixed-dose combination medication used for the treatment of high cholesterol. It is a combination of bempedoic acid and ezetimibe.