PMID- 25849526 OWN - NLM STAT- MEDLINE DCOM- 20151020 LR - 20150507 IS - 1872-7972 (Electronic) IS - 0304-3940 (Linking) VI - 595 DP - 2015 May 19 TI - A novel brain-derived neurotrophic factor-modulating peptide attenuates Abeta1-42-induced neurotoxicity in vitro. PG - 63-8 LID - S0304-3940(15)00279-7 [pii] LID - 10.1016/j.neulet.2015.03.070 [doi] AB - 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 (Abeta). 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 Abeta1-42-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. CI - Copyright (c) 2015. Published by Elsevier Ireland Ltd. FAU - Shin, Min-Kyoo AU - Shin MK AD - 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. FAU - Kim, Hong-Gi AU - Kim HG AD - Department of Biological Sciences, Sungkyunkwan University, 300 Chunchun-Dong, Jangan-Gu, Suwon, Gyeonggi-Do 440-746, South Korea. FAU - Kim, Kil-Lyong AU - Kim KL AD - Department of Biological Sciences, Sungkyunkwan University, 300 Chunchun-Dong, Jangan-Gu, Suwon, Gyeonggi-Do 440-746, South Korea. Electronic address: kimkl@skku.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150404 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Amyloid beta-Peptides) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neuroprotective Agents) RN - 0 (Oligopeptides) RN - 0 (Peptide Fragments) RN - 0 (amyloid beta-protein (1-42)) RN - 0 (methionyl-aspartyl-glycine) SB - IM MH - Amyloid beta-Peptides/*metabolism/toxicity MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cell Death/drug effects MH - Cell Line, Tumor MH - Humans MH - Neurons/cytology/drug effects MH - Neuroprotective Agents/*pharmacology MH - Oligopeptides/*pharmacology MH - Peptide Fragments/*metabolism/toxicity MH - Primary Cell Culture MH - Rats, Sprague-Dawley OTO - NOTNLM OT - Alzheimer's disease OT - Amyloid-beta OT - Brain-derived neurotrophic factor OT - Neuroprotection OT - Peptide EDAT- 2015/04/08 06:00 MHDA- 2015/10/21 06:00 CRDT- 2015/04/08 06:00 PHST- 2014/09/24 00:00 [received] PHST- 2015/02/11 00:00 [revised] PHST- 2015/03/25 00:00 [accepted] PHST- 2015/04/08 06:00 [entrez] PHST- 2015/04/08 06:00 [pubmed] PHST- 2015/10/21 06:00 [medline] AID - S0304-3940(15)00279-7 [pii] AID - 10.1016/j.neulet.2015.03.070 [doi] PST - ppublish SO - Neurosci Lett. 2015 May 19;595:63-8. doi: 10.1016/j.neulet.2015.03.070. Epub 2015 Apr 4.