A novel brain-derived neurotrophic factor-modulating peptide attenuates A beta(1-42)-induced neurotoxicity in vitro

作者：Shin Min Kyoo; Kim Hong Gi; Kim Kil Lyong^*

来源：Neuroscience Letters, 2015, 595: 63-68.

DOI：10.1016/j.neulet.2015.03.070

• Brain-derived neurotrophic factor
• Alzheimer's disease
• Amyloid-beta
• Neuroprotection
• Peptide

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 (A beta). 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 1 pM 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 A beta(1-42)-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.

• 出版日期2015-5-19