The novel vaccine peptide GV1001 effectively blocks beta-amyloid toxicity by mimicking the extra-telomeric functions of human telomerase reverse transcriptase

Abstract

GV1001 is a 16-amino-acid vaccine peptide derived from the human telomerase reverse transcriptase sequence. We investigated the effects of GV1001 against beta-amyloid (A beta) oligomer-induced neurotoxicity in rat neural stem cells (NSCs). Primary culture NSCs were treated with several concentrations of GV1001 and/or A beta(25-35) oligomer for 48 hours. GV1001 protected NSCs against the A beta(25-35) oligomer in a concentration-dependent manner. A beta(25-35) concentration dependently decreased viability, proliferation, and mobilization of NSCs and GV1001 treatment restored the cells to wild-type levels. A beta(25-35) increased free radical levels in rat NSCs while combined treatment with GV1001 significantly reduced these levels. In addition, GV1001 treatment of A beta(25-35) injured NSCs increased the expression level of survival-related proteins, including mitochondria-associated survival proteins, and decreased the levels of death and inflammation-related proteins, including mitochondria-associated death proteins. Together, these results suggest that GV1001 possesses neuroprotective effects against A beta(25-35) oligomer in NSCs and that these effects are mediated through mimicking the extra-telomeric functions of human telomerase reverse transcriptase, including the induction of cellular proliferation, anti-apoptotic effects, mitochondrial stabilization, and anti-aging and anti-oxidant effects.