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Brain-Specific Aminopeptidase: From Enkephalinase to Protector Against Neurodegeneration

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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.

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  1. Peptide Research Laboratory, Neurochemistry Division, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, 10962, USA

    Koon-Sea Hui

  2. Department of Psychiatry, New York University Medical School, New York, NY, 10016, USA

    Koon-Sea Hui

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Special issue in honor of Naren Banik.

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Hui, KS. Brain-Specific Aminopeptidase: From Enkephalinase to Protector Against Neurodegeneration. Neurochem Res 32, 2062–2071 (2007). https://doi.org/10.1007/s11064-007-9356-3

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