12 - Homeobox Peptides as a Novel Class of Neurotrophic Molecules

Abstract

Publisher Summary This chapter discusses homeobox peptides as a novel class of neurotrophic molecules. In the laboratory, a strategy was devised to study the role of homeoproteins in embryonic rat neurons at the single cell level. Its principle is to simultaneously disturb the action of several homeoproteins by introducing the 60 amino-acid long homeodomain of Antennapedia (pAntp) into the nuclei of nerve cells in culture. Homeodomains such as pAntp do not transactivate by themselves but efficiently compete with homeoproteins of the same class, independently of species specificity. It was observed that the mechanical introduction of pAntp into rat embryonic neurons increases neurite growth. It was also found that pAntp added to the culture medium was able to translocate across the neuronal membrane and to accumulate in the nuclei, thus producing neurotrophic effects similar to those observed upon direct introduction in the cells. The peptide captured by the neurons and recovered, undegraded, from nuclear extracts was still capable of displacing endogenous nuclear proteins from a specific homeoprotein class I target sequence.