NPC1
Encyclopedia
Niemann-Pick disease, type C1 also known as NPC1 is a protein
which in humans is encoded by the NPC1 gene
.
NPC1 was identified as the gene that when mutated, results in Niemann-Pick disease, type C
. NPC1 encodes a putative integral membrane protein
containing sequence motif
s consistent with a role in intracellular transport of cholesterol
to post-lysosomal
destinations.
It has been associated with obesity
.
Mice carrying a mutation in this gene are resistant to infection by the Ebola virus
(it is not yet known whether this mutated gene might offer similar protection against Ebola's cousin in the filovirus group, the Marburg virus
). Agents that can cause a short-term alteration (permanent alterations normally cause Niemann-Pick disease
, a disorder of cholesterol metabolism) in this cellular protein similar to this scenario might be tolerated long enough to be a potential treatment for the as-yet virtually untreatable and very deadly hemorrhagic virus. Research and development of such agents is now actively being pursued. This is being done with the assistance of personnel and resources from the Harvard University Medical School-based National Small Molecule Screening Laboratory, the Whitehead Institute for Biomedical Research, Harvard affiliate Brigham and Women's Hospital
, the Albert Einstein College of Medicine
, and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). These findings, reported in September 2011, build on a 2005 paper that found that Ebola exploits the cathepsin B
protein, apparently in order to subsequently bind with normal NPC1.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the NPC1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
NPC1 was identified as the gene that when mutated, results in Niemann-Pick disease, type C
Niemann-Pick disease, type C
Niemann-Pick type C is a lysosomal storage disease associated with mutations in NPC1 and NPC2 genes. Niemann-Pick Type C strikes an estimated 1:150,000 people...
. NPC1 encodes a putative integral membrane protein
Integral membrane protein
An integral membrane protein is a protein molecule that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein...
containing sequence motif
Sequence motif
In genetics, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and has, or is conjectured to have, a biological significance...
s consistent with a role in intracellular transport of cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
to post-lysosomal
Lysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
destinations.
It has been associated with obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
.
Mice carrying a mutation in this gene are resistant to infection by the Ebola virus
Ebola virus
Ebola virus causes severe disease in humans and in nonhuman primates in the form of viral hemorrhagic fever. EBOV is a Select Agent, World Health Organization Risk Group 4 Pathogen , National Institutes of Health/National Institute of Allergy and Infectious Diseases Category A Priority Pathogen,...
(it is not yet known whether this mutated gene might offer similar protection against Ebola's cousin in the filovirus group, the Marburg virus
Marburg virus
Marburg virus disease is the name for the human disease caused by any of the two marburgviruses Marburg virus and Ravn virus...
). Agents that can cause a short-term alteration (permanent alterations normally cause Niemann-Pick disease
Niemann-Pick disease
Niemann–Pick disease refers to a group of fatal inherited metabolic disorders that are included in the larger family of lysosomal storage diseases .-Signs and symptoms:Symptoms are related to the organs in which they accumulate...
, a disorder of cholesterol metabolism) in this cellular protein similar to this scenario might be tolerated long enough to be a potential treatment for the as-yet virtually untreatable and very deadly hemorrhagic virus. Research and development of such agents is now actively being pursued. This is being done with the assistance of personnel and resources from the Harvard University Medical School-based National Small Molecule Screening Laboratory, the Whitehead Institute for Biomedical Research, Harvard affiliate Brigham and Women's Hospital
Brigham and Women's Hospital
Brigham and Women's Hospital is the largest hospital of the Longwood Medical and Academic Area in Boston, Massachusetts. It is directly adjacent to Harvard Medical School of which it is the second largest teaching affiliate with 793 beds...
, the Albert Einstein College of Medicine
Albert Einstein College of Medicine
Albert Einstein College of Medicine is a graduate school of Yeshiva University. It is a not-for-profit, private, nonsectarian medical school located on the Jack and Pearl Resnick Campus in the Morris Park neighborhood of the borough of the Bronx of New York City...
, and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). These findings, reported in September 2011, build on a 2005 paper that found that Ebola exploits the cathepsin B
Cathepsin B
Cathepsin B is an enzymatic protein belonging to the peptidase families. In humans, it is coded by the CTSB gene.- Function :...
protein, apparently in order to subsequently bind with normal NPC1.