Amyloid beta (A4) precursor protein (APP) is a transmembrane protein that plays a crucial role in the development and function of the nervous system. It is widely expressed in various tissues, with higher concentrations found in the brain . The human recombinant form of this protein is used extensively in research to understand its structure, function, and role in diseases, particularly Alzheimer’s disease.
APP is a cell surface receptor that performs several physiological functions on the surface of neurons. These functions include neurite growth, neuronal adhesion, and axonogenesis . The protein undergoes sequential proteolytic processing by enzymes known as secretases, leading to the generation of amyloid-beta (Aβ) peptides of different lengths .
The proteolytic processing of APP involves two main pathways: the non-amyloidogenic pathway and the amyloidogenic pathway. In the non-amyloidogenic pathway, APP is cleaved by α-secretase, resulting in the release of a soluble APP fragment (sAPPα) and a membrane-bound C-terminal fragment (CTFα). This pathway precludes the formation of Aβ peptides.
In the amyloidogenic pathway, APP is first cleaved by β-secretase, producing a soluble APP fragment (sAPPβ) and a membrane-bound C-terminal fragment (CTFβ). The CTFβ is then further cleaved by γ-secretase, resulting in the release of Aβ peptides . These Aβ peptides can aggregate to form amyloid plaques, which are a hallmark of Alzheimer’s disease .
Aβ peptides are the major component of amyloid plaques found in the brains of Alzheimer’s patients . The aggregation of these peptides is believed to play a central role in the pathogenesis of Alzheimer’s disease. Mutations in the APP gene have been implicated in autosomal dominant Alzheimer’s disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy) .
Human recombinant APP is used in various research applications to study its structure, function, and role in disease. It is also used to develop therapeutic strategies aimed at modulating APP processing and reducing Aβ peptide formation. Understanding the mechanisms underlying APP processing and Aβ aggregation is crucial for developing effective treatments for Alzheimer’s disease.