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Protease Pathways in Peptide Neurotransmission and Neurodegenerative Diseases

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Cellular and Molecular Neurobiology Aims and scope Submit manuscript

1. Recent research demonstrates the critical importance of neuroproteases for the production of peptide neurotransmitters, and for the production of toxic peptides in major neurodegenerative diseases that include Alzheimer's (AD) and Huntington's diseases. This review describes the strategies utilized to identify the appropriate proteases responsible for producing active peptides for neurotransmission, with application of such approaches for defining protease mechanisms in neurodegenerative diseases.

2. Integration of multidisciplinary approaches in neurobiology, biochemistry, chemistry, proteomics, molecular biology, and genetics has been utilized for neuroprotease studies. These investigations have identified secretory vesicle cathepsin L for the production of the enkephalin opioid peptide neurotransmitter and other neuropeptides. Furthermore, new results using these strategies have identified secretory vesicle cathepsin B for the production of β-amyloid (Aβ) in the major regulated secretory pathway that provides activity-dependent secretion of Aβ peptides, which accumulate in AD.

3. CNS neuroproteases that participate in peptide neurotransmission and in neurodegenerative diseases represent new candidate drug targets that may be explored in future research for the development of novel therapeutic agents for neurological conditions.

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ACKNOWLEDGMENTS

The author appreciates support of this research from the National Institutes of Health, American Life Science Pharmaceuticals (ALSP) Inc., and the Hereditary Disease Foundation. Dr. V. Hook holds equity in ALSP Inc., and serves on the Scientific Advisory Board of ALSP. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies.

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  1. Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive MC 0744, La Jolla, CA, 92093-0324, USA

    Vivian Y. H. Hook

  2. Departments of Neurosciences and Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, 92093-0324, USA

    Vivian Y. H. Hook

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Correspondence to Vivian Y. H. Hook.

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Hook, V.Y.H. Protease Pathways in Peptide Neurotransmission and Neurodegenerative Diseases. Cell Mol Neurobiol 26, 447–467 (2006). https://doi.org/10.1007/s10571-006-9047-7

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