The Amino-Terminal Region of Amyloid Precursor Protein Is Responsible for Neurite Outgrowth in Rat Neocortical Explant Culture

Abstract

We have previously shown that secreted forms of β-amyloid precursor protein (APPss) promote neurite outgrowth in embryonic rat neocortical explant culture. To determine the region of APPsresponsible for its biological activity, we produced both amino- and carboxyl-terminal regions of APPsusing a yeast expression system. The purified fragment corresponding to the amino-terminal region (NAPP) enhanced neurite outgrowth of neocortical explants, but the carboxyl-terminal region fragment did not. The neurite-promoting activity of full length APPsand NAPP was blocked by the antibody, 22C11, specific for the amino-terminal region, and the 16-mer peptide of epitope for 22C11 also enhanced neurite outgrowth. However, the 17-mer peptide which contains RERMS sequence did not enhance the neurite outgrowth, but promoted the survival of neocortical neurons in dissociated culture. These findings suggested that the amino-terminal region is responsible for the neurite-promoting activity of APPss.