Company description
The Aβ region of APP contains a sequence of 42-43 amino acid residues, partially located in the extracellular domain and partially in the transmembrane domain of APP. APP is cleaved by three types of proteases, called α-,β-and γ-secretase. Proteolytic cleavage of amyloid from amyloid precursor (APP) by APP secretase is a key event in the pathogenesis of Alzheimer’s disease (AD). The α-secretase cleaves APP within the amyloid sequence, while the β- and γ-secretase cleave at the N- and C-termini, respectively. The transmembrane aspartyl protease BACE has been identified as a beta-secretase, and several proteases (ADAM-10, TACE, PC7) may be α-secretase. β-secretase and γ-secretase are involved in the production of β-amyloid components in senile plaques in the brains of patients with Alzheimer’s disease, and have driven the main research work to design these selective protease inhibitors. Interestingly, γ-secretase cleaves several proteins, including Notch, E-cadherin, CD44 and ErbB-4 (erythroblast leukemia virus oncogene homolog 4), which are important regulators of angiogenesis. The β-amyloid precursor protein, which is cleaved by β-secretase and γ-secretase to produce β-amyloid, is highly expressed in the endothelium of neovascularization, suggesting that it may play a role in angiogenesis.
