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

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• 作者：Hyun-Hee Park^a ; ¹ ; Kyu-Yong Lee^a ; ¹ ; Sangjae Kim^b ; Jessica Woojin Lee^b ; Na-Young Choi^c ; Eun-Hye Lee^c ; Young Joo Lee^a ; Sang-Hun Lee^d ; Seong-Ho Koh^a ; ^c ; ^{ksh213@hanyang.ac.kr" class="auth_mail}
• 关键词：Peptide ; Vaccine ; GV1001 ; 尾-Amyloid ; Oligomer ; Neural stem cells
• 刊名：Neurobiology of Aging
• 出版年：June, 2014
• 年：2014
• 卷：35
• 期：6
• 页码：1255-1274
• 全文大小：5982 K

文摘

GV1001 is a 16-amino-acid vaccine peptide derived from the human telomerase reverse transcriptase sequence. We investigated the effects of GV1001 against 尾-amyloid (A尾) oligomer-induced neurotoxicity in rat neural stem cells (NSCs). Primary culture NSCs were treated with several concentrations of GV1001 and/or A尾_25-35 oligomer for 48聽hours. GV1001 protected NSCs against the A尾_25-35 oligomer in a concentration-dependent manner. A尾_25-35 concentration dependently decreased viability, proliferation, and mobilization of NSCs and GV1001 treatment restored the cells to wild-type levels. A尾_25-35 increased free radical levels in rat NSCs while combined treatment with GV1001 significantly reduced these levels. In addition, GV1001 treatment of A尾_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尾_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.