CYTOTOXIC PEPTIDES AND PEPTIDOMIMETICS BASED THEREON, AND METHODS FOR USE THEREOF

摘要

In accordance with the present invention, it has been discovered that the beta -amyloid precursor protein (APP), and two APP-like proteins (APLP1 and APLP2) are proteolytically cleaved by caspases in the C terminus to generate an approximately 31 amino acid peptide. It has been further discovered that the resultant C-terminal peptide is a potent inducer of apoptosis. Both caspase-cleaved APP and activated caspase-9 is present in brains of Alzheimer's disease patients but not in control brains. These findings indicate that caspase cleavage of APP and APP-like proteins leads to the generation of apoptotic peptides, which may contribute to the neuronal death associated with Alzheimer's disease. Accordingly, there are provided compositions and methods for modulating apoptosis.