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Amyloid precursor protein (APP) has many functions and regulations. This protein is involved in neural development. Many may know it for its involvement in the pathology of Alzheimer disease as well as other neurodegenerative diseases. However, APP is a developmental gene. This gene contains many functions such as regulating neurons, their differentiation and the regulation of migration. This gene is also associated in neurite outgrowth and the regulation of synaptic activity (1). Despite knowledge of these functions, many functions of APP is still unclear (2). 
APP is a member of type 1 membrane proteins which also includes amyloid precursor -like proteins 1 and 2, APLP1 and APLP2 (human), Appl (fly), and apl-1 (worm). They each contain a large extracellular N-terminal domain and a small cytoplasmic domain. However, only APP contains the amyloid-? (A?), a 39- to 43-amino acid peptide, the non-properly formed peptide is known for causing neurodegenerative diseases. (3). APP is structured and can be cleaved by ?, ? and ?-secretases; these cleavage sites are only involved in the full-length APP. Additionally, APP undergoes amyloidogenic or non-amyloidogenic activities. In the amyloidogenic, cleavage by ?-secretase produces the development of soluble APP? and ?APP-CTF. The activity of ?-secretase on ?APP-CTF allows A? to form from the amyloid precursor protein intracellular domain (AICD). However, In the non-amyloidogenic, cleavage by ?-secretase hinders the development of A?; ?-secretase cleaves in the A? sequence, this increases the amount of sAPP? as well as ?APP-CT, which is then cleaved by ?-secretase and results in the outcome of the P3 peptide and AICD (1).
APP contains many functions. One of the many functions that APP consists of is that it has been shown to activate neurite outgrowth. This is done with the regulation of APP expression during neuronal maturation (2). Studies have shown evidence of the function of APP in increasing neurite length and branching, whether its independently or as a result of its influence with other proteins. Furthermore, APP products such as sAPP?/? and AICD in generating neurite outgrowth have also been reported (1). Additionally, studies have also demonstrated a function for APP in regulating stem cells. APP encourages the differentiation of neural stem cells into astrocytic lineage (2). In human embryonic stem cells, the over expression of APP causes fast and strong differentiation (1). Another function of this protein that has been found in some studies was that APP was demonstrated to withstand rapid axonal transport to synaptic sites. APP was also encountered in vesicular sections of dendrites and axons. This suggests an important function for APP in synaptic function (1). These functions of APP are shown to be involved in neural development. Therefore, APP is a complex protein that posses many functions, many of which are still not very well understood. 
Fig 1: Summary of the roles of APP and its metabolites during neural development  

As mentioned earlier APP is found to be involved in neural development. The functions discussed above have shown how. During early development, the expression pattern of APP in neuroblasts and neurons in the neural tube suggests a role in neurogenesis, including neural proliferation, differentiation and axonal outgrowth (7). Figure 1 shows neural development from early stages. It shows how APP and APP metabolites play important roles during the different stages of neural development. The stages range from neural proliferation to the formation of a functional synapse. The metabolites that posses an upward arrow represent a positive effect, whereas the metabolites with unknown effects are indicated with a question mark (1). There is still much to learn how APP is involved in neural development. Many studies and experiments are currently being done to study the functions of this protein.
Several studies have shown that various kinases control the processing of APP. However, the mechanism is unknown. Kinases regulate APP processing indirectly. They do so by phosphorylating proteins associated in the intracellular trafficking. PKC and PKA have been shown to phosphorylate a closely related trans-Golgi network protein, by adjusting the formation of secretory vesicles which contain mature APP. PKC and PKA may apply their end result by phosphorylating substrates in the APP secretory pathway, which may affect proteasome function. However, it is unknown whether this phosphorylation changes the formation of A?. Although, PKC may alter ?-secretase-mediated activity by extending the time APP spends in the cell surface caveolae. This thereby increases the time spent in contact with ?-secretase (8). 
APP processing was found to be regulated by neurotransmitters. This involved the over expression of acetylcholine receptors. This increased the amount of sAPP released and decreased the amount of A? production. Additionally, the control of sAPP secretion has appeared to occur in cell lines indicating their normal supply of acetylcholine receptors. Regulation of sAPP release was seen to occur for other neurotransmitters reacting at G protein-coupled receptors that may include the metabotropic glutamate receptor and serotonin receptors (8). Regulation of sAPP is also involved in the release of activation of ligand-gated channels. Neurotransmitter regulation of APP processing has revolved mainly on cholinergic and glutamatergic innervation. Additionally, the release of acetylcholine and sAPP, effects were halted by the blockage of voltage-sensitive sodium channels with tetrodotoxin. Therefore, studies suggest that activation of neurotransmitter receptors illustrates the regulation of A? production (8). 
APP is involved in the pathology of some neurodegenerative diseases such as Alzheimer disease. APP and its cleavage product, A?, have been extensively studied in relation to Alzheimer disease (5). It is believed that the A? peptide can induce neurotoxic responses in the brain which may lead to Alzheimer disease (6). Additionally amyloid plaques are formed and accumulate preferably in the cerebral cortex. There are two types, dense and diffuse (7). The amyloid cascade hypothesis suggests that A? accumulation  in the brain is the primary event during Alzheimer disease pathology. This hypothesis explains that the imbalance between A? productions and clearance is the main cause of this disease. This imbalance gradually increases the A?42 levels in the brain, resulting in oligomerization which initiates synaptic dysfunction and neuronal loss. Futhermore, increased deposition of A? may trigger alterations and formation of neurofibrillary tangles (7). 
The pathological characteristics of Alzheimer disease are known to be amyloid plaques and neurofibrillary tangles which are composed of A? and hyperphosphorylated tau. In addition, large amounts of neuritic degeneration have been noticed including a loss of cholinergic fibers. As mentioned, the A? peptide is thought to play an important role in Alzheimer disease pathogenesis, however this is due to the mutations in the gene that are associated to in forms of early-onset Alzheimer disease. These mutations can either cause a high production of A? or it can increase the more fibrillogenic A? 

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