Prolyl oligopeptidase (EC, 3.4.21.26), also known as prolyl endopeptidase, is the only serine protease that catalyses the hydrolysis of peptides at the C-terminal side of L-proline residues. It is widely distributed in mammals and can be purified from various organs, including the brain.
The enzyme plays an important role in the breakdown of proline-containing neuropeptides related to learning and memory functions (Wilk, S., Life Sci., 33, 2149–2157 (1983); O'Leary, R. M., O'Connor, B., J. Neurochem., 65, 953–963 (1995)). Compounds capable of inhibiting prolyl oligopeptidase are effective for preventing experimental amnesia induced by scopolamine in rats, inferring that prolyl oligopeptidase inhibitors have functions in the fixation of memory (Yoshimoto, T., Kado, K., Matsubara, F., Koryama, N., Kaneto, H., Tsuru, D., J. Pharmacobio-Dyn., 10, 730–735 (1987)).
In recent years it has been found that β-amyloid protein shows neurotoxic action in in vitro and in vivo experiments and that it plays an important role in the onset of Alzheimer's disease. In view of the hypothesis that substance P can suppress neurotoxic action of β-amyloid protein (Kowall, N. W., Beal, M. F., Busciglio, J., Duffy, L. K., Yankner, B. A., Proc. Natl. Acad. Sci. USA, 88, 7247–7251 (1991)), it is speculated that prolyl oligopeptidase inhibitors that inhibit also metabolism of substance P can make an effective drug for the treatment of Alzheimer's disease.