In continuation of our studies, we are measuring the breakdown of proteins and peptides in the brain. The long-term aim is to understand the detailed mechanisms and their control, and then to influence peptide hydrolysis in the brain in a therapeutically useful way. In the coming year we will continue to isolate and study the properties of brain peptidases. In previous publications we have reported some results of separation, and also some properties of the enzymes. We now use brain peptides, MIF, enkephalins as substrates, and a few model di- and tri-peptides. In protein breakdown we plan to confirm our recent studies finding increased breakdown in immature brain; we will focus on the breakdown of purified brain proteins (tubulin, enolases, GAFP) by purified cathepsin D and cathepsin M. This work will require specific peptide inhibitors for identification and purification of the enzymes.