Amyloid precursor protein proteolytic cleavage

Human amyloid precursor protein Proteolytic cleavage by y-secretase 115, 116... 

Amyloid precursor protein (APP) is the precursor of (3-amyloid, the main component of senile plaques found in the brain of Alzheimer patients. The production of (3-amyloid from APP to the cells from abnormal proteolytic cleavage of the amyloid precursor protein. Enzymes involved in this cleavage may be suitable targets for the therapy of Alzheimer s disease. 

Most cases of AzD show cerebrovascular amyloid deposits and the amyloid protein of senile plaques is the same as that found in blood vessels. It is referred to as )S-amyloid protein and is part of a 695, 751 or 770 amino-acid amyloid precursor protein APP, which is a transmembrane protein and although its precise function is not clear, it is widely distributed and APP knock-out mice show reduced motor function. Normally so-called short 40 amino-acid-soluble derivatives of APP are produced by proteolytic cleavage of APP within the j] (A4) amino-acid sequence but APP can also be cleaved... 

Strong evidence suggests that the main constituent of the plaque, P-amyloid peptide (AP), exerts a prominent role in the cause, initiation and progression of AD. Thus AD appears to arise from the abnormal deposition of a protein. Ap is derived from proteolytic cleavage of amyloid precursor protein (APP), an integral membrane protein. APP is cleaved by the sequential actions of three unique proteases, called a-, p-, and y-secretases. Each secretase cleaves at a unique site (see figure 8.7). 

Ap is the principal constituent of senile plaques found in AD patients brains and as such has made it a key suspect in the search for causative agents of AD. Ap is a 39-43 residue peptide (Fig. 1) that is derived from the proteolytic cleavage of the amyloid precursor protein APP, a type I integral membrane protein. APP is processed by three proteases a-, P-, and... 

The y9-amyloid is produced by proteolytic cleavage of amyloid precursor protein (APP) first by f - and then by y-secretases (Fig. 4.9). 

Secretases, three proteases (a-, /3- and y-secretase) implicated in the etiology of Alzheimer s disease. They are responsible for the formation of amyloid-/3 by proteolytic cleavage of the precursor protein APR [W. P. Esler, M. S. Wolfe, Science 2001, 293, 1449]. 

Gervais, F.G., Xu, D., Robertson, G.S., et al. (1999) Involvement of caspases in proteolytic cleavage of Alzheimer s amyloid-beta precursor protein and amyloidogenic A-beta peptide formation. Cell, 97, 395 06. 

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