Secretase Inhibitors

Secretases are made up of three main subclasses of protease enzymes: α, β, and γ.. All three groups of secretases play a pivotal role in the processing of Amyloid proteins thereby cementing their importance in the development and progression of Alzheimer's disease (AD). α- Secretases cleave the amyloid precursor protein (APP) within its transmembrane region generating non-amyloidogenic APP (default normal processing of APP). α-Secretases belong to the ADAM (a disintegrin and metalloprotease domain) family of proteases. The activity of α-secretases has been implicated in the regulation of learning and memory, maturation of MHC class I proteins etc. β-Secretases are aspartic-acid proteases involved in the formation of myelin sheaths in peripheral nerve cells. β -secretase 1 (BACE1) or beta-site APP cleaving enzyme 1 is responsible for the generation of the 40-42 amino acid-long fibrillar amyloid-β peptides that form aggregates/plaques in the brain of Alzheimer's patients. Drugs or inhibitors to block this enzyme could prevent the accumulation of beta-amyloid and may help slow or stop Alzheimers disease. γ-Secretases are multi-subunit protease complexes within the membrane that cleave single-pass transmembrane proteins at residues within the transmembrane domain. Amyloidogenic peptides are generated by the conjugated action of γ- and β-secretases. γ-Secretases are also critical in the processing of several other type I integral membrane proteins e.g. Notch, E-cadherin, CD44 etc. The scientific understanding of β- and γ-secretases can provide a framework for rational drug design to treat Alzheimer's disease and other protein aggregation diseases. Compounds targeting each of the three secretases are currently in clinical trials by various Pharmaceutical companies. BioVision provides a compilation of different inhibitors for the pathologically important β- and γ-secretase enzymes.