APP : amyloid beta precursor protein

Description

The APP (amyloid beta precursor protein) is a protein-coding gene located on chromosome 21.

The APP gene provides instructions for making a protein called amyloid precursor protein. This protein is found in many tissues and organs, including the brain and spinal cord (central nervous system). Little is known about the function of amyloid precursor protein. Researchers speculate that it may bind to other proteins on the surface of cells or help cells attach to one another. Studies suggest that in the brain, it helps direct the movement (migration) of nerve cells (neurons) during early development.Amyloid precursor protein is cut by enzymes to create smaller fragments (peptides), some of which are released outside the cell. Two of these fragments are called soluble amyloid precursor protein (sAPP) and amyloid beta (β) peptide. Recent evidence suggests that sAPP has growth-promoting properties and may play a role in the formation of neurons in the brain both before and after birth. The sAPP peptide may also control the function of certain other proteins by turning off (inhibiting) their activity. Amyloid β peptide is likely involved in the ability of neurons to change and adapt over time (plasticity). Other functions of sAPP and amyloid β peptide are under investigation.

The APP gene encodes a cell surface receptor that plays a role in neurite growth, neuronal adhesion, and axonogenesis. Interactions between APP molecules on neighboring cells promote synaptogenesis. APP is involved in cell mobility and transcription regulation, and can activate transcription through binding to APBB1-KAT5, while inhibiting Notch signaling by interacting with Numb. APP couples to apoptosis-inducing pathways, such as those mediated by G(o) and JIP, and inhibits G(o) alpha ATPase activity. Acting as a kinesin I membrane receptor, APP mediates axonal transport of beta-secretase and presenilin 1, contributing to axonal anterograde transport of cargo towards synapses. APP is involved in copper homeostasis and oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or through Cu(2+)-mediated low-density lipoprotein oxidation. APP regulates neurite outgrowth by binding to components of the extracellular matrix, such as heparin and collagen I and IV. Splice isoforms containing the BPTI domain exhibit protease inhibitor activity. APP induces an AGER-dependent pathway, activating p38 MAPK, leading to internalization of amyloid-beta peptide and mitochondrial dysfunction in cultured cortical neurons. APP provides Cu(2+) ions for GPC1, essential for nitric oxide (NO) release and subsequent degradation of heparan sulfate chains on GPC1.

APP is also known as AAA, ABETA, ABPP, AD1, APPI, CTFgamma, CVAP, PN-II, PN2, alpha-sAPP, preA4.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing