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Protease Mechanisms for the Biosynthesis of Peptide Neurotransmitters


Neuropeptides are peptide neurotransmitters and hormones that play an integral role in mediating neurotransmission, cell-cell communication amongst neurons, and modulate functions in the neuroendocrine system. In particular, this thesis focuses on opioid neuropeptides which are involved in addiction, chronic pain, analgesia, cognitive function as well as the proteases that are associated with their biosynthesis. Cathepsin L, Cathepsin V, PC1, and PC2 are proteases found to process these endogenous opioid proneuropeptides at dibasic residues. Elucidating the properties of these proteases and how they influence the cleavages of these proneuropeptides may hold potential for developing future inhibitors that regulate these proteases and neuropeptides. These findings can have clinical therapeutic application for diseases and impairments related to these proteases and peptides such as neurological and mental disorders, chronic pain, and more.

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