• Min-Kyoo Shin, Hong-Gi Kim, and Kil-Lyong Kim.
• 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.
• Neurosci. Lett. 2015 May 19;595:63-8.

AbstractBrain-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.Copyright © 2015. Published by Elsevier Ireland Ltd.

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