title: A novel brain-derived neurotrophic factor-modulating peptide attenuates Aβ1-42-induced neurotoxicity in vitro.
abstract: Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which plays important roles in learning and memory formation and in protecting neurons from diverse neurotoxic insults, such as amyloid-beta (Aβ). Since BDNF expression is decreased in patients with Alzheimer's disease, various strategies have attempted to increase BDNF levels. In a previous study, we screened and identified a novel BDNF-modulating peptide (consisting of methionine-valine-glycine, named Neuropep-1) by a positional scanning-synthetic peptide combinatorial library (PS-SPCL). Neuropep-1 exhibited neuroprotective effects against in vitro and in vivo Alzheimer's disease models. Based on the previous PS-SPCL data, we modified the amino acid sequence of Neuropep-1 in this study to identify a more potent novel BDNF-modulating peptide. By replacing the valine in the second position with aspartic acid, the resulting Neuropep-4 was found to be highly effective in inducing BDNF expression even at concentrations of 1pM in the SH-SY5Y cell line and rat primary cortical neurons. In addition, among the tested peptides, Neuropep-4 provided neurons with the strongest protection against oligomeric and/or fibrillar Aβ1-42-induced cell death through BDNF upregulation. These results suggest the potential of Neuropep-4 as a therapeutic candidate for treating neurodegenerative diseases, such as AD.
authors: Department of Biological Sciences, Sungkyunkwan University, 300 Chunchun-Dong, Jangan-Gu, Suwon, Gyeonggi-Do 440-746, South Korea; Institute of Basic Science, Sungkyunkwan University, 300 Chunchun-Dong, Jangan-Gu, Suwon, Gyeonggi-Do 440-746, South Korea.
authors: Min-Kyoo
authors: MK
authors: Shin
authors: Department of Biological Sciences, Sungkyunkwan University, 300 Chunchun-Dong, Jangan-Gu, Suwon, Gyeonggi-Do 440-746, South Korea.
authors: Hong-Gi
authors: HG
authors: Kim
authors: Department of Biological Sciences, Sungkyunkwan University, 300 Chunchun-Dong, Jangan-Gu, Suwon, Gyeonggi-Do 440-746, South Korea. Electronic address: kimkl@skku.edu.
authors: Kil-Lyong
authors: KL
authors: Kim
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity; D061251:Primary Cell Culture; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D009842:Oligopeptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C000602142:methionyl-aspartyl-glycine
keywords: Alzheimer’s disease; Amyloid-beta; Brain-derived neurotrophic factor; Neuroprotection; Peptide