Neuropeptide-processing enzymes: Applications for drug discovery
Journal Title: The AAPS Journal - Year 2005, Vol 7, Issue 2
Abstract
Neuropeptides serve many important roles in communication between cells and are an attractive target for drug discovery. Neuropeptides are produced from precursor proteins by selective cleavages at specific sites, and are then broken down by further cleavages. In general, the biosynthetic cleavages occur within the cell and the degradative cleavages occur postsecretion, although there are exceptions where intracellular processing leads to inactivation, or extracellular processing leads to activation of a particular neuropeptide. A relatively small number of peptidases are responsible for processing the majority of neuropeptides, both inside and outside of the cell. Thus, inhibition of any one enzyme will lead to a broad effect on several different neuropeptides and this makes it unlikely that such inhibitors would be useful therapeutics. However, studies with mutant animals that lack functional peptide-processing enzymes have facilitated the discovery of novel neuropeptides, many of which may be appropriate targets for therapeutics.
Authors and Affiliations
Lloyd D. Fricker
Novel Molecular Targets of Azadirachta indica Associated with Inhibition of Tumor Growth in Prostate Cancer
The online version of this article (doi:10.1208/s12248-011-9279-4) contains supplementary material, which is available to authorized users.
Tissue Penetration of a Novel Spectinamide Antibiotic for the Treatment of Tuberculosis
The online version of this article (doi:10.1208/s12248-016-9900-7) contains supplementary material, which is available to authorized users.
Antinociceptive Effects of Racemic AM1241 and Its Chirally Synthesized Enantiomers: Lack of Dependence upon Opioid Receptor Activation
The online version of this article (doi:10.1208/s12248-009-9170-8) contains supplementary material, which is available to authorized users.
BCS Biowaivers: Similarities and Differences Among EMA, FDA, and WHO Requirements
The Biopharmaceutics Classification System (BCS), based on aqueous solubility and intestinal permeability, has enjoyed wide use since 1995 as a mechanism for waiving in vivo bioavailability and bioequivalence studies. In...
Non-Arrhenius Protein Aggregation
Protein aggregation presents one of the key challenges in the development of protein biotherapeutics. It affects not only product quality but also potentially impacts safety, as protein aggregates have been shown to be l...