Brain-specific aminopeptidase: from enkephalinase to protector against neurodegeneration

Neurochem Res. 2007 Dec;32(12):2062-71. doi: 10.1007/s11064-007-9356-3. Epub 2007 May 3.

Abstract

The major breakthrough discovery of enkephalins as endogenous opiates led our attempts to determine their inactivation mechanisms. Because the NH2-terminal tyrosine is absolutely necessary for the neuropeptides to exert analgesic effects, and aminopeptidase activities are extraordinarily high in the brain, a specific "amino-enkephalinase" should exist. Several aminopeptidases were identified in the central nervous system during the search. In fact, our laboratory found two novel neuron-specific aminopeptidases: NAP and NAP-2. NAP is the only functionally active brain-specific enzyme known. Its synaptic location coupled with its limited substrate specificity could constitute a "functional" specificity and contribute to enkephalin-specific functions. In addition, NAP was found to be essential for neuron growth, differentiation, and death. Thus, aminopeptidases are likely important for mental health and neurological diseases. Recently, puromycin-sensitive aminopeptidase (PSA) was identified as a modifier of tau-induced neurodegeneration. Because the enzymatic similarity between PSA and NAP, we believe that the depletion of NAP in Alzheimer's disease (AD) brains plays a causal role in the development of AD pathology. Therefore, use of the puromycin-sensitive neuron-aminopeptidase NAP could provide neuroprotective mechanisms in AD and similar neurodegenerative diseases.

Publication types

  • Review

MeSH terms

  • Aminopeptidases / metabolism
  • Aminopeptidases / physiology*
  • Animals
  • Brain / enzymology*
  • Enkephalins / metabolism
  • Humans
  • Hydrolysis
  • Neprilysin / physiology*
  • Neurodegenerative Diseases / pathology*
  • Neurons / enzymology
  • Opioid Peptides / metabolism

Substances

  • Enkephalins
  • Opioid Peptides
  • Aminopeptidases
  • Neprilysin