A Group of Weakly Bound to Neurons Extracellular Metallopeptidases (NEMPs).

We have found that isolated from mammalian brain (rat, bovine) axonal endings (synaptosomes) degrade peptides of different composition. With the use of low concentration of non ionic detergent Triton X-100 (0.05-0.1 %) four low specific metallopeptidases were detached from synaptosomes. These peptidases were named Neuronal EctoMetalloPeptidases (NEMPs). Using specially designed test-peptides they were characterized as: carboxypeptidase (NEMP1), aminopeptidase (NEMP2) and endopeptidases NEMP3 and NEMP4. NEMPs are true peptidases (oligopeptidases), because they are able efficiently degrade peptides containing less than 40 amino acid residues. Specific properties of some NEMPs were revealed. NEMP1 is a small protein (molecular mass of about 10 kDa), which tends to dynamic oligomerization. NEMP3 needs activation. Some amino acids activate this enzyme. As far as we know, these properties were not ascribed to the known similarly localized peptidases. A possible physiological function of low specific NEMPs is participation in control of wide range of neuropeptides secreted in the synaptic cleft. However, NEMPs also due to their low specificity can destroy introduced in brain therapeutic peptides. The data obtained in this study open new opportunities for the protection of synthetic therapeutic peptides in brain and, possibly, in other tissues.