Amyloid b/A4 Protein Precursor (APP) Fragments

DefinitionDiscovery
Amyloid precursor protein (APP) is a singleIn 1984, Glenner and Wong purified APP derived from
transmembrane protein that undergoes sequentialthe twisted beta-pleated sheet fibrils present in
proteolysis to generate multiple peptides, including thecerebrovascular amyloidoses and in the amyloid
amyloid beta peptide the major component of theplaques associated with Alzheimer disease1.
senile plaques that are diagnostic hallmarks ofStructural characteristics
Alzheimer disease (AD).APP is a 110-130 kDa, transmembrane cell surface
Discoveryglycoprotein, which contains N and O, linked sugars.
In 1984, Glenner and Wong purified APP derived fromThe largest region of the molecule is the extracellular
the twisted beta-pleated sheet fibrils present indomain. This domain contains a cysteine-rich region of
cerebrovascular amyloidoses and in the amyloidabout 200 amino acids and is at the N-terminus of
plaques associated with Alzheimer disease1.the protein. It has a single membrane-spanning
Structural characteristicsdomain towards the carboxyl terminus and a short
APP is a 110-130 kDa, transmembrane cell surfacecytoplasmic
glycoprotein, which contains N and O, linked sugars.Function
The largest region of the molecule is the extracellularAPP plays major roles in the regulation of several
domain. This domain contains a cysteine-rich region ofimportant cellular functions, especially in the nervous
about 200 amino acids and is at the N-terminus ofsystem, where it is involved in synaptogenesis and
the protein. It has a single membrane-spanningsynaptic plasticity. The secreted extracellular domain
domain towards the carboxyl terminus and a shortof APP, sAPPa, acts as a growth factor for many
cytoplasmic tail. APP contains a domain very similar totypes of cells and promotes neuritogenesis in
the Kunitz family of serine protease inhibitors and thepost-mitotic neurons4.
APP protein is homologous to protein proteaseReference:
nexin-II2.1. Furuya H, Sasaki H, Goto I, Wong CW, Glenner GG,
Mode of actionSakaki Y. (1988). Amyloid beta-protein gene
APP plays an essential role in the reduction of copperduplication is not common in Alzheimer's disease:
II to copper I. This electron transfer reaction isanalysis by polymorphic restriction fragments.
involved in the formation of reactive oxygen speciesBiochem Biophys Res Commun., 150 (1):75-81.
(e.g., superoxide radical and hydroxyl radical)3 which2. Ponte P, Gonzalez-DeWhitt P, Schilling J, Miller J, Hsu
are extremely reactive with many different cellularD, Greenberg B, Davis K, Wallace W, Lieberburg I,
components. These reactions can produce largeFuller F (1988). A new A4 amyloid mRNA contains a
amounts of damage and ultimately results in celldomain homologous to serine proteinase inhibitors.
death.Nature, 331 (6156):525-527.
Definition3. Camakaris J, Voskoboinik I, Mercer JF (1999).
Amyloid precursor protein (APP) is a singleMolecular mechanisms of copper homeostasis.
transmembrane protein that undergoes sequentialBiochem Biophys Res Commun, 261:225-232.
proteolysis to generate multiple peptides, including the4. Gralle M, Ferreira ST (2007). Structure and
amyloid beta peptide the major component of thefunctions of the human amyloid precursor protein: the
senile plaques that are diagnostic hallmarks ofwhole is more than the sum of its parts. Prog
Alzheimer disease (AD).Neurobiol, 82 (1):11-32.