APP (amyloid precursor protein) is a transmembrane glycoprotein measuring from 100 to 140 kDa. Protein precursor is a biological term, which refers to a class of protein-peptide chains synthesized by genes coding on the long arm of chromosome 21. Because of its hydrolysis break, a peptide chain called amyloid is composed of 40 to 42 amino acids, so it is called amyloid precursor and APP for short. APP is found in various body tissues, and due to the different number of amino acids that constitute the peptide chain, at least three different APP types have been found, and APP695 is found in the brain. Under normal conditions, APP will be enzymatically decomposed into smaller fragments, including soluble APP alpha and soluble APP β, which can modulate neuronal function and survival, and APP β will be further processed and cleaved into Amyloid β. In the natural, non-pathological state, Amyloid β is in a random coiled conformation. In the pathological state, the protein transforms into a secondary β -folded structure and spontaneously accumulates into an insoluble precipitate.

The function of APP under normal conditions is to participate in the growth, proliferation, differentiation, and survival of neural cells. APP has also been implicated in physiological processes such as synapse formation and maintenance, neuronal migration and adhesion, and apoptosis. Moreover, APP can be enzymatically resolved into smaller fragments, some of which are neuroprotective. APP and its metabolites are essential for normal brain physiology. APP contributes to the regulation of synaptic transmission, plasticity, and calcium homeostasis. It plays an important role in development and plays a neuroprotective role. Of particular importance is the soluble secreted fragment APPs alpha, which mediates many of its physiological effects, generally counteracting the effects of the APP-derived small peptide A β.

The APP ortholog APPL directly interacts with G alpha o in motor neurons, thus APPL-G alpha o signaling regulates the response of migrating neurons to ligands encountered in the developing nervous system. APP signaling provides a mechanism to integrate APP-regulated stress and survival responses by modulating the PI3K / Akt pathway by transducing the neuroprotective effects of the soluble sAPPalphafragment. The C-terminal fragment (CTF) derived from APP interacts with Galphas, and thus CTF-Galphas signaling can promote neurite outgrowth through an adenylylate cyclase / PKA-dependent pathway. The effect of APP-EXO is most likely mediated by a reduction in the expression level of exosomal miR-185-5p. Meanwhile, the UTR ′ of the APP transcript was bound to miR-185-5p, thus inhibiting the sorting of miR-185-5p from the exosome.

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