University of California, San Diego | Skaggs School of Pharmacy and Pharmaceutical Sciences

Reviews: Proteases for the Biosynthesis of Active Peptides in Neurotransmission and Neurodegenerative Disease


Hook, V., Funkelstein, L., Lu, D., Bark, S., Wegrzyn, J., and Hwang, S.-R. (2007) Proteases for processing proneuropeptides into peptide neurotransmitters and hormones. Annu. Rev. Pharmacol. Tox., in press.


Hook, V. (2006) Unique neuronal functions of cathepsin L and cathepsin B in secretory vesicles: biosynthesis of peptides in neurotransmission and neurodegenerative disease. Biol. Chem. 387, 1429–1439.


Hook, V., Yasothornsrikul, S., Greenbaum, D., Medzihradszky, K.F., Troutner, K., Toneff, T., Bundey, R., Logrinova, A., Reinheckel, T., Peters, C., and Bogyo, M. (2004) Cathepsin L and Arg/Lys aminopeptidase: a distinct prohormone processing pathway for the biosynthesis of peptide neurotransmitters and hormones. Biol. Chem. 385, 473–480.

Neuropeptides: Peptide Neurotransmitters


Hwang, S-R., Garza, C., Mosier, C., Toneff, T., Wunderlich, E., Goldsmith, P., and Hook, V. (2007) Cathepsin L expression is directed to secretory vesicles for enkephalin neuropeptide biosynthesis and secretion. J. Biol. Chem. 282, 9556-9563.


Hwang, S.-R., O’Neill, A., Bark, S., Foulon, T., and Hook, V. (2007) Secretory vesicle aminopeptidase B related to neuropeptide processing: molecular identification and subcellular localization to enkephalin- and NPY-containing chromaffin granules. J. Neurochem. 100, 1340-1350.


Yasothornsrikul, S., Greenbaum, D., Medzihradszky, K.F., Toneff, T., Bundey, R., Miller, R., Schilling, B., Petermann, I., Dehnert, J., Logvinova, A., Goldsmith, P., Neveu, J.M., Lane, W.S., Gibson, B., Reinheckel, T., Peters, C., Bogyo, M., and Hook, V. (2003) Cathepsin L in secretory vesicles functions as a prohormone-processing enzyme for production of the enkephalin peptide neurotransmitter. Proc. Natl. Acad. Sci. U S A 100, 9590–9595.

Toxic Peptides and Proteases in Neurodegenerative Diseases: Alzheimer’s Disease and Huntington’s disease.


Hook, V., Kindy, M., and Hook, G. (2007) Cysteine protease inhibitors effectively reduce in vivo levels of brain beta-amyloid related to Alzheimer’s disease. Biol. Chem. 388, 247-252.


Hook, V., Toneff, T., Bogyo, M., Greenbaum, D., Medzihradszky, K.F., Neveu, J., Lane, W., Hook, G., and Reisine, T. (2005) Inhibition of cathepsin B reduces ?-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate ?-secretase of Alzheimer’s disease. Biol. Chem. 386, 931–940


Mende-Mueller, L.M., Toneff, T., Hwang, S-R., Chesselet, M-F., and Hook, V.Y.H. (2001) Tissue-specific proteolysis of huntingtin (htt) in human brain: evidence of enhanced levels of N- and C-terminal htt fragments in Huntington’s disease striatum. J. Neurosci. 21, 1830–1837.

Proteomics of Secretory Vesicles


Wegrzyn, J., Lee, J., Neveu, J.M., Lane, W.S., and Hook, V. (2007) Proteomics of neuroendocrine secretory vesicles reveal distinct functional systems for biosynthesis and exocytosis of peptide hormones and neurotransmitters. J. Proteome Research 6, 1652-1665.


Bark, S.J. and Hook, V. (2007) The future of proteomic analysis in biological systems and molecular medicine. Molecular BioSystems 3, 14-17.