Neurochemical Research

, Volume 32, Issue 12, pp 2062–2071 | Cite as

Brain-Specific Aminopeptidase: From Enkephalinase to Protector Against Neurodegeneration

Original Paper

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.

Keywords

Neuron-specific aminopeptidase Neuropeptides Enkephalins Neurodegeneration Alzheimer’s disease 

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Peptide Research Laboratory, Neurochemistry DivisionNathan S. Kline Institute for Psychiatric ResearchOrangeburgUSA
  2. 2.Department of PsychiatryNew York University Medical SchoolNew YorkUSA

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