Neuropeptidases

Neuropeptides are neurotransmitters and modulators distributed in the central nervous system (CNS) and peripheral nervous system. Their abnormalities cause neurological and mental diseases. Neuropeptidases are enzymes crucial for the biosynthesis and biodegradation of neuropeptides. We here focus on the peptidases involved in the metabolism of the well-studied opioid peptides. Bioactive enkephalins are formed from propeptides by processing enzymes—prohormone thiol protease, prohormone convertase 1 and 2 (PC 1 and 2), carboxypeptidase H/E, and Arg/Lys aminopeptidase. After they exert their biological effects, enkephalins are likely to be inactivated by degrading enzymes—angiotensin-converting enzyme (ACE), aminopeptidase N (APN), puromycin-sensitive aminopeptidase (PSA), and endopeptidase 24.11. Recently, a neuron-specific aminopeptidase (NAP), which was a putative enkephalin-inactivating enzyme at the synapses, was found. Neuropeptidases are useful drug targets and their inhibitors can be therapeutic. Synthetic anti-enkephalinases and anti-aminopeptidases are being developed. They are potent analgesics but have fewer side effects than the opiates.