PROFILING OF ENDOGENOUS PEPTIDES AS A TOOL FOR STUDYING DEVELOPMENT AND NEUROLOGICAL DISEASE

The use of a method to follow changes in endogenous peptide production , as they occur in biological studies, is an excellent complement to o ther molecular techniques. It has the unique ability to characterize p eptides that have been produced from protein precursors, and instrumen tation is available that provides high resolution peptide separations that are quantitative, sensitive, and amenable to automation. All tiss ues express a large number of peptide species that can be visualized, or profiled on chromatographic separations using reverse-phase high-pe rformance liquid chromatography. This large number of peptides offers many potential molecules that can be used to identify biological mecha nisms associated with experimental paradigms. Peptide analysis has bee n used successfully in many types of studies. In this review, we outli ne our experience in using peptides as biological markers and provide a description of the evolution of peptide profiling in our laboratorie s. Peptide expression has been used in studies ranging from how brain regions develop to identifying changes in disease processes including Alzheimer's disease and models of stroke. Some of the findings provide d by these studies have been new pathways of peptide processing and th e identification of accelerated proteolysis on proteins such as hemogl obin as a function of Alzheimer's disease and brain insult. Peptide pr ofiling has also proven to be an excellent technique for studying many well-known nervous system proteins including calmodulin, PEP-19, myel in basic protein, cytoskeletal proteins, and others. It is the purpose of this review to describe our experience using the technique and to highlight improvements that have added to the power of the approach. P eptide analysis and the expansion in the instrumentation that can. det ect peptides will no doubt make these types of studies a powerful addi tion to our molecular armamentarium for conducting biological studies. (C) 1997 John Wiley & Sons, Inc.