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


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Proteases for Neutrotransmission and Neurodegenerative Diseases: Applications to Therapeutic Agents

The focus of our research is to understand how proteases and protease inhibitors are responsible for (1) multi-step proteolytic pathways required for converting precursor proteins into active neuropeptides that function as neurotransmitters, and (2) the protease mechanisms responsible for neurological diseases, including chronic pain, Alzheimer's and Huntington's diseases, and (3) proteomic approaches for elucidation of protease components as potential drug targets and therapeutics. These disciplines strive to understand the proteolytic controls involved in generating 'beneficial' peptides that promote health, and 'detrimental' peptides in disease. (more)



Proteomics is the study of proteins and their interactions with in complex biological systems. While this field is often associated with mass spectrometry, it is more useful to consier the proteomics in the context of an objective: to identify and understand the molecular basis of health and disease at the protein level in vivo. Achieving this objective will require (1) technological developments to resolve current instrument limitations and (2) multidisciplinary integration of biological and protein analysis technologies to answer important questions in both the biological sciences and molecular medicine. (more)

Publications In Press:

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.

Bark, S.J., and Hook, V. (2007) Differentical recovery of peptides from sample tubes and the reproducibility of quantitative proteomic data. J. Proteome Research.


Hook, G., Hook, V.Y.H., and Kindy, M. (2007) Cysteine protease inhibitors reduce brain beta-amyloid and beta-secrease activity in vivo and are potential Alzheimer's disease therapeutics. Biol. Chem. 388, 979-983.

Hwang, S.R., and Hook, V.Y.H. (2007) Multiple domains of endopin 2A for serpin cross-class inhibition of papain. Arch. Biochem. Biophys. 46, 219-224.