Production and Catabolism of Amyloid Peptides in Alzheimer's Disease.

Production and Catabolism of Amyloid Peptides in Alzheimer's Disease. Senile plaques that accumulate in cortical and sub-cortical areas of Alzheimer's disease (AD)-affected brains are mainly composed of a set of hydrophobic and aggregated peptides referred to as amyloid beta-peptides (A beta). These peptides derive from the proteolytic processing of a transmembrane precursor, the beta-amyloid precursor protein (beta APP) that undergoes subsequent cleavages by beta- and gamma-secretases, respectively. Another enzyme called a-secretase cleaves beta APP in the middle of its A beta sequence and thereby, lowers its production. Once produced, A beta peptides can be cleared off by neuropeptidases, mainly insulin-degrading enzyme and neprilysin, or, alternatively, can be biotransformed upon N-terminal truncation by exopeptidases and subsequent cyclisation of the glutamate in position 3. Here, we will describe the nature of the various proteolytic activities documented above and we will discuss briefly their advantages and drawbacks as putative therapeutic targets in AD.