Novel vaccine peptide GV1001 effectively blocks β-amyloid toxicity by mimicking the extra-telomeric functions of human telomerase reverse transcriptase.
GV1001 is a 16-amino-acid vaccine peptide derived from the human telomerase reverse transcriptase sequence. We investigated the effects of GV1001 against β-amyloid (Aβ) oligomer-induced neurotoxicity in rat neural stem cells (NSCs). Primary culture NSCs were treated with several concentrations of GV1001 and/or Aβ₂₅₋₃₅ oligomer for 48 hours. GV1001 protected NSCs against the Aβ₂₅₋₃₅ oligomer in a concentration-dependent manner. Aβ₂₅₋₃₅ concentration dependently decreased viability, proliferation, and mobilization of NSCs and GV1001 treatment restored the cells to wild-type levels. Aβ₂₅₋₃₅ increased free radical levels in rat NSCs while combined treatment with GV1001 significantly reduced these levels. In addition, GV1001 treatment of Aβ₂₅₋₃₅-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 Aβ₂₅₋₃₅ 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.
Department of Neurology, Hanyang University College of Medicine, Guri, Gyeonggi, Korea.
Hyun-Hee
HH
Park
Department of Neurology, Hanyang University College of Medicine, Guri, Gyeonggi, Korea.
Kyu-Yong
KY
Lee
Department of Neuroscience, KAEL-Gemvax Co, Ltd, Seoul, Korea.
Sangjae
S
Kim
Department of Neuroscience, KAEL-Gemvax Co, Ltd, Seoul, Korea.
Jessica Woojin
JW
Lee
Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science & Engineering, Seoul, Korea.
Na-Young
NY
Choi
Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science & Engineering, Seoul, Korea.
Eun-Hye
EH
Lee
Department of Neurology, Hanyang University College of Medicine, Guri, Gyeonggi, Korea.
Young Joo
YJ
Lee
Department of Biochemistry and Molecular Biology, Hanyang University College of Medicine, Seoul, Korea.
Sang-Hun
SH
Lee
Department of Neurology, Hanyang University College of Medicine, Guri, Gyeonggi, Korea; Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science & Engineering, Seoul, Korea. Electronic address: ksh213@hanyang.ac.kr.
Seong-Ho
SH
Koh
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D058632:Neuroprostanes; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity*; D051381:Rats; D019098:Telomerase / Q000737:chemistry* / Q000494:pharmacology / Q000502:physiology
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D024101:Mitochondrial Proteins; D058632:Neuroprostanes; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C514987:GV1001 peptide; D019098:Telomerase
GV1001; Neural stem cells; Oligomer; Peptide; Vaccine; β-Amyloid