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Secretase

 

 
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Secretase
 
 
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Secretases are enzymes that "snip" pieces off a longer protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
 that is embedded in the cell membrane
Cell membrane

The cell membrane is the interface between the cellular machinery inside the cell and the fluid outside.It is a semipermeable lipid bilayer found in all cell ....
. Among other roles in the cell
Cell (biology)

The cell is the structural and functional unit of all known Life organisms. It is the smallest unit of an organism that is classified as living, and is often called the building bricks of life....
, secretases act on the amyloid precursor protein
Amyloid precursor protein

Amyloid precursor protein is an integral membrane protein expressed in many biological tissue and concentrated in the synapses of neurons. Its primary function is not known, though it has been implicated as a regulator of synapse formation and neural plasticity....
 (APP) to cleave the protein into three fragments. Sequential cleavage by ß-secretase
Beta-secretase

?-Secretase ? also called BACE1 or memapsin-2 ? is an aspartic-acid protease important in the pathogenesis of Alzheimer's disease, and in the formation of myelin sheaths in peripheral nerve cells....
 (BACE) and ?-secretase produces the amyloid-ß peptide fragment that aggregates into clumps called "plaques" in the brains
Brains

Brains is predominantly the plural of brain.Brains may also refer to:* The Brains , Atlanta band who did the original version of the song "Money Changes Everything"...
 of Alzheimer's disease
Alzheimer's disease

Alzheimer's disease , also called Alzheimer disease, Senile Dementia of the Alzheimer Type or simply Alzheimer's, is the most common form of dementia....
 patients.






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Secretases are enzymes that "snip" pieces off a longer protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
 that is embedded in the cell membrane
Cell membrane

The cell membrane is the interface between the cellular machinery inside the cell and the fluid outside.It is a semipermeable lipid bilayer found in all cell ....
.
App Processing
Among other roles in the cell
Cell (biology)

The cell is the structural and functional unit of all known Life organisms. It is the smallest unit of an organism that is classified as living, and is often called the building bricks of life....
, secretases act on the amyloid precursor protein
Amyloid precursor protein

Amyloid precursor protein is an integral membrane protein expressed in many biological tissue and concentrated in the synapses of neurons. Its primary function is not known, though it has been implicated as a regulator of synapse formation and neural plasticity....
 (APP) to cleave the protein into three fragments. Sequential cleavage by ß-secretase
Beta-secretase

?-Secretase ? also called BACE1 or memapsin-2 ? is an aspartic-acid protease important in the pathogenesis of Alzheimer's disease, and in the formation of myelin sheaths in peripheral nerve cells....
 (BACE) and ?-secretase produces the amyloid-ß peptide fragment that aggregates into clumps called "plaques" in the brains
Brains

Brains is predominantly the plural of brain.Brains may also refer to:* The Brains , Atlanta band who did the original version of the song "Money Changes Everything"...
 of Alzheimer's disease
Alzheimer's disease

Alzheimer's disease , also called Alzheimer disease, Senile Dementia of the Alzheimer Type or simply Alzheimer's, is the most common form of dementia....
 patients. If a-secretase acts on APP first instead of BACE, no amyloid-ß is formed because a-secretase recognizes a target protein sequence closer to the cell surface than BACE. The non-pathogenic middle fragment formed by an a/? cleavage sequence is called P3.

Structure

The structure
Protein structure

Proteins are an important class of biological macromolecules present in all biological organisms, made up of such chemical element as carbon,hydrogen, nitrogen, oxygen, and sulphur....
 of the three secretases varies widely.

  • The a-secretase gene
    Gene

    A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cell and pass genetic trait to offspring....
     has not been conclusively identified but is believed to be a metalloproteinase
    Metalloproteinase

    Metalloproteinases constitute a family of enzymes from the group of proteinases, classified by the nature of the most prominent functional group in their active site....
    .


  • BACE is a transmembrane protein with an extracellular aspartic acid protease domain
    Domain (biology)

    In Biology taxonomy, a domain is the highest taxonomic rank of organisms, higher than a Kingdom . According to the three-domain system of Carl Woese, introduced in 1990, the Tree of life consists of three domains: Archaea, Bacteria and Eukaryota....
    .


  • ?-secretase is actually a protein complex
    Protein complex

    A multiprotein complex is a group of two or more proteins. Protein complexes are a form of quaternary structure. Proteins in a protein complex are linked by non-covalent protein-protein interactions, and different protein complexes have different degrees of stability over time....
     containing presenilin
    Presenilin

    Presenilins are a family of related multi-pass transmembrane proteins that function as a part of the gamma-secretase protease complex. Vertebrates have two presenilin genes, called PSEN1 that encodes presenilin 1 and PSEN2 that codes for presenilin 2 ....
    , nicastrin
    Nicastrin

    Nicastrin, also known as NCSTN, is a protein which in humans is encoded by the NCSTN gene.Nicastrin is a protein that is part of the gamma secretase protein complex, which is one of the proteases involved in processing amyloid precursor protein to the short Alzheimer's disease-associated peptide amyloid beta....
    , ACH-1, and PEN-2
    PEN-2

    PEN-2 is a protein that is a regulatory component of the gamma secretase complex, a protease complex responsible for proteolysis of transmembrane proteins such as the Notch pathway and amyloid precursor protein ....
    . Presenilin is believed to harbor the protease domain and represents an important example of an uncommon type of protease
    Protease

    A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain, which form a molecule of protein....
     that cleaves targets within the cell membrane.


Function

Besides their involvement in the pathogenesis of Alzheimer's, these proteins also have other functional roles in the cell.

?-secretase plays a critical role in developmental signalling
Signal transduction

In biology, 'signal transduction' refers to any process by which a cell converts one kind of signal or stimulus into another. Most processes of signal transduction involve ordered sequences of biochemistry chemical reaction inside the cell, which are carried out by enzymes, activated by Second messenger systems, resulting in a signal tran...
 by the transmembrane receptor
Transmembrane receptor

Transmembrane receptors are integral membrane proteins, which reside and operate typically within a cell's plasma membrane, but also in the biological membrane of some subcellular compartments and organelles....
 Notch
Notch signaling

The Notch signaling pathway is a highly conserved cell signaling system present in most multicellular organisms. Notch is present in all metazoans, and vertebrates possess four different notch receptors, referred to as NOTCH1, NOTCH2, Notch 3, and NOTCH4....
, freeing the cytoplasmic tail of Notch to travel to the cell nucleus
Cell nucleus

In cell biology, the nucleus , also sometimes referred to as the "control center", is a membrane-enclosed organelle found in all eukaryote cell ....
 to act as a transcription factor
Transcription factor

In the field of molecular biology, a transcription factor is a protein that binds to specific DNA sequence and thereby controls the transfer of genetic information from DNA to RNA....
.

Although BACE cleaves the extracellular domains of several transmembrane proteins, its physiological function remains unknown.

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