Gamma-secretase and Its Substrates: a Bioinformatics Approach

Gamma-secretase is an enzymatic complex critical to amyloid formation and other important pathophysiological processes. Non-specific gamma-secretase inhibitors are not ideal for intervention of familial Alzheimer¿s disease. Also gamma-secretase cleaves a variety of substrates. But different sites are cleaved even in a single substrate and no consensus sequence for cleavage by gamma-secretase is identified. We hypothesize that consensus compositional sequence in components of gamma-secretase and its substrates should exist during gamma-secretase regulation and specific gammasecretase inhibitor based on such consensus sequence may act as a therapeutic intervention for familial Alzheimer¿s disease. There are two stages in our research. First, We find the candidates by the methods of bioinformatics. Then, we use the traditional biological methods to verify the critical role of the candidates including the protein purification, recognition, and functional domain interaction. The book can serve as reference for computational biology-oriented professionals in advanced research development.