APP Specific Neutra™ Antibody Products
Product listAmyloid beta precursor protein (APP), also known as AD1, is a cell surface receptor. APP is overexpressed in normal amniocytes and cerebrospinal fluid. Due to its critical role in the pathogenesis of Alzheimer's disease (AD), many strategies hold great promise for the exploration of disease-modifying AD therapies via targeting the amyloidogenic processing of APP.
Its Gene ID: 351, UniProtKB ID: P05067, and OMIM ID: 104760.
Structures and Signaling Partners of APP
APP and its two mammalian homologs, APLP-1 and APLP-2, have similar primary structures and conserved extracellular domains. APP binds its ligands with or without the disulfide-bridged heparin recognition domains. APP protein possesses conserved cytosolic domains and has a protein-protein interaction network as shown in Figure 1.
Fig.1 The receptor-like architecture and signaling partners of membrane-bound APP.1
Proteolysis of APP
With a large extracellular domain, APP is regulated by multiple factors and is cleaved by three membrane-bound proteases α-, β-, and γ- secretase, which is shown in Figure 2.
- The deposition of amyloid β peptide (Αβ), a small peptide produced by the amyloidogenic processing of APP, is regarded as the key factor in the neurodegeneration of AD.
- The soluble extracellular p3 peptide is generated by the nonamyloidogenic proteolysis of the majority of APP in the healthy state.
Fig.2 Amyloidogenic and non-amyloidogenic proteolysis of APP.2
Clinical Strategies for the Amyloidogenic Process of APP
Interference with the amyloidogenic process of APP is one of the most important strategies to modulate Aβ production. The detailed strategies are shown in Figure 3.
- The β-site APP-cleaving enzyme 1 (BACE1) is a prerequisite for the γ-secretase cleavage of APP. Small molecule BACE1 inhibitors could effectively reduce Aβ levels in the brain and cerebrospinal fluid.
- Targeting compounds, inhibitors, and modulators of γ-secretase could reduce the risk of AD with lower amyloid burden.
- Stimulation of α-secretase with related metalloproteases can lead to a significant reduction of Αβ production. The related metalloproteases appear to exert the α-secretase activity.
Fig.3 Drug discovery strategies based on proteolysis of APP.2
Creative Biolabs offers anti-APP antibodies for various applications. These antibodies have high specificity and affinity to APP protein, which are suitable for immunoassays.
REFERENCES
- Deyts, et al. "APP receptor? To be or not to be." Trends in pharmacological sciences 37.5 (2016): 390-411.
- Zhao, Jing, et al. "Targeting amyloidogenic processing of APP in Alzheimer's disease." Frontiers in molecular neuroscience 13 (2020): 137.
