CHYMOTRYPSIN-LIKE PROTEASES AND THEIR INHIBITORS

摘要

Disclosed is the identification, characterization, and purification of two chymotrypsin-like serine proteases characteristic of AD, called "chymase" and "multicatalytic protease". Both chymase and the multicatalytic protease have an enzymatic activity capable of cleaving between Met and Asp, which activity is required to generate beta-amyloid. Methods are provided for quantifying the activities of chymase and the multicatalytic protease in brain (and other tissues samples and fluids) to allow diagnosis of AD, and for development of inhibitors as therapeutic agents to slow progress of the disease. Novel compositions have been prepared and identified as inhibitors of the two enzymes. Substrates are also disclosed. Methods are provided for the treatment of AD and the identification of proteases capable of generating beta-amyloid protein. Methods are also provided for cloning and sequencing of human brain chymase and the multicatalytic protease, and the preparation of nucleic acid and antibody probes to them.