Amyloid Synthesis

Amyloid Synthesis

Amyloid beta (Aβ) is a short peptide contains 37 to 43 amino acids and is well known for its hypothesized role in causing pathogenesis of AD, since one of the main hallmarks of AD is the accumulation of fibrillogenic Aβ in the grey matter of the brain (14–15). Meanwhile, over 90% of AD patients have cerebral amyloid angiopathy (CAA) which is characterized by the deposition of Aβ in capillaries, arteries, and arterioles (16–17). CAA causes the degeneration of smooth muscle cells and leads haemorrhages (17).

Aβ is generated by proteolytic processing from its precursor, the amyloid precursor protein (APP), which is a type–I oriented membrane protein and its splicing variants include APP695, APP714, APP751, APP770 (18–21). The isoforms APP751 ... Show more content on Helpwriting.net ...The processing of APP involves three proteases, α–, β–, and γ–secretases and two processing pathways, the amyloidogenic pathway and the anti–amyloidogenic pathway as shown in Figure 2 (14, 23). The Aβ is generated in amyloidogenic pathway which is mediated by β–, and γ–secretases (14). The β– secretase first sheds the ectodomain of APP and generates the APP carboxy–terminal fragment (βCTF) (14). Then the γ–secretase cuts at the transmembrane region of βCTF and releases the Aβ into the extracellular fluids like cerebrospinal fluid or plasma (14, 24). In the anti–amyloidogenic pathway α–secretase first cuts at the middle region of Aβ so a trauncated APP CTF (αCTF) is generated and after the transmembrane cut of γ–secretase, a truncated Aβ peptide is released (p3) (Figure 2; 25). The amyloidogenic and anti–amyloidogenic competes with each other (26–27). In addition, when the γ–secretase cuts at the transmembrane region of APP, the cut site is not restricted to a single position. The γ–secretase first cuts at

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