THE AMINO-TERMINAL REGION OF AMYLOID PRECURSOR PROTEIN IS RESPONSIBLEFOR NEURITE OUTGROWTH IN RAT NEOCORTICAL EXPLANT CULTURE

We have previously shown that secreted forms of beta-amyloid precursor protein (APP(s)s) promote neurite outgrowth in embryonic rat neocorti cal explant culture. To determine the region of APP(s) responsible for its biological activity, we produced both amino- and carboxyl-termina l regions of APP(s) using a yeast expression system. The purified frag ment corresponding to the amino-terminal region (NAPP) enhanced neurit e outgrowth of neocortical explants, but the carboxyl-terminal region fragment did not. The neurite-promoting activity of full length APP(s) and NAPP was blocked by the antibody, 22C11, specific for the amino-t erminal region, and the 16-mer peptide of epitope for 22C11 also enhan ced neurite outgrowth, However, the 17-mer peptide which contains RERM S sequence did not enhance the neurite outgrowth, but promoted the sur vival of neocortical neurons in dissociated culture. These findings su ggested that the amino-terminal region is responsible for the neurite- promoting activity of APP(s)S. (C) 1997 Academic Press.