Cytosolic Oligopeptidases: Features and Possible Physiopathological Roles in the Immune and Nervous Systems

M.A.F. Hayashi; F.C.V. Portaro; A.C.M. Camargo

Abstract

During the course of evolution, invertebrates and vertebrates have maintained common signaling molecules, such as neuropeptides that participate in a number of physiological processes. The first step of this process includes the action of prohormone convertases on the precursor proteins in order to generate the bioactive molecules. Once the neuropeptide is produced and released, it promotes the stimulation of target cells, which subsequently are desensitized to permanently maintain sensitivity to various internal or external stimuli. The desensitization process depends upon a second step in the neuropeptide metabolism that regulates its concentration in the biophase and/or controlling the stoichiometry of various peptide products. Among the putative enzymes involved in the second step of neuropeptide metabolism there are the tissue oligopeptidases: endooligopeptidase A (EOPA), endooligopeptidase B or prolyloligopeptidase (PO), thimet oligopeptidase (TOP) and neurolysin (NL) are the best characterized. Recent evidences suggest that the role of the mammalian cytosolic oligopeptidases may not be restricted to their proteolytic activities. The discovery that the EOPA (also known as NUDEL) is an essential protein for the development of the CNS suggested an entirely distinct physiological role for this protein. Another oligopeptidase, the thimet oligopeptidase, was shown to be involved in the MHC class I antigen presentation, not only as a proteolytic enzyme but also as a peptide chaperone. Both activities are likely to play essential roles in the cellular immune defense. In this article we review the properties of cytosolic oligopeptidases, both as peptidases and as participants in the physiological and pathological processes of the nervous tissue and the immune defense.

Keywords: oligopeptidases, nudel, mhc class I epitopes, endooligopeptidase a, neurolysin, thimet oligopeptidase, nervous tissue, neuropeptides