Novel vaccine peptide GV1001 effectively blocks β-amyloid toxicity by mimicking the extra-telomeric functions of human telomerase reverse transcriptase

  • Neurobiol Aging. 2014 Jun;35(6):1255-74. doi: 10.1016/j.neurobiolaging.2013.12.015.
Hyun-Hee Park  1 Kyu-Yong Lee  1 Sangjae Kim  2 Jessica Woojin Lee  2 Na-Young Choi  3 Eun-Hye Lee  3 Young Joo Lee  1 Sang-Hun Lee  4 Seong-Ho Koh  5
Affiliations
  • 1. Department of Neurology, Hanyang University College of Medicine, Guri, Gyeonggi, Korea.
  • 2. Department of Neuroscience, KAEL-Gemvax Co, Ltd, Seoul, Korea.
  • 3. Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science & Engineering, Seoul, Korea.
  • 4. Department of Biochemistry and Molecular Biology, Hanyang University College of Medicine, Seoul, Korea.
  • 5. 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: [email protected].
Abstract

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.

Keywords
GV1001; Neural stem cells; Oligomer; Peptide; Vaccine; β-Amyloid.
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