Niemann-Pick C1-Like 1 (NPC1L1) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
found on the
gastrointestinal tract's epithelial
Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
cells
as well as in
hepatocytes
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass.
These cells are involved in:
* Protein synthesis
* Protein storage
* Transformation of carbohydrates
* Synthesis of cholesterol, bile ...
.
Specifically, it appears to bind to a critical
mediator
Mediation is a structured, voluntary process for resolving disputes, facilitated by a neutral third party known as the mediator. It is a structured, interactive process where an independent third party, the mediator, assists disputing parties ...
of
cholesterol
Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils.
Cholesterol is biosynthesis, biosynthesized by all anima ...
absorption.
The drug
ezetimibe
Ezetimibe, sold under the brand name Zetia among others, 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 ...
inhibits NPC1L1 causing a reduction in cholesterol
absorption
Absorption may refer to:
Chemistry and biology
*Absorption (biology), digestion
**Absorption (small intestine)
*Absorption (chemistry), diffusion of particles of gas or liquid into liquid or solid materials
*Absorption (skin), a route by which su ...
, resulting in a
blood cholesterol
Blood lipids (or blood fats) are lipids in the blood, either free or bound to other molecules. They are mostly transported in a phospholipid capsule, and the type of protein embedded in this outer shell determines the fate of the particle and its ...
reduction of 15-20%.
in the NPC1L1
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
could be associated with non-response to ezetimibe treatment. One study found that people with
inactivating mutations in the NPC1L1 gene had a lower
LDL cholesterol level, as well as an around 50% reduction in the risk of
coronary heart disease
Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of cardiovascular disease, heart disease involving Ischemia, the reduction of blood flow to the cardiac muscle due to a build-up ...
.
NPC1L1 has been shown to be an
accessory receptor for
hepatitis C virus
The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family ''Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepatoc ...
entry into cells, and thus ezetimibe might be used as a therapeutic strategy.
As
cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
appeared more frequently in patients treated with
simvastatin
Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease hyperlipidemia, elevated lipid levels. It is also used to decrease t ...
-
ezetimibe
Ezetimibe, sold under the brand name Zetia among others, 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 ...
combination therapy in one clinical trial,
it had been
hypothesized that NPC1L1 inhibition by ezetimibe might be associated with an increased cancer risk.
However, a
meta-analysis
Meta-analysis is a method of synthesis of quantitative data from multiple independent studies addressing a common research question. An important part of this method involves computing a combined effect size across all of the studies. As such, th ...
of ezetimibe
clinical data showed no increase in the risk of cancer from treatment with ezetimibe.
References
External links
*
* {{PDBe-KB2, Q9UHC9, Human NPC1-like intracellular cholesterol transporter 1