A novel brain-derived neurotrophic factor-modulating peptide attenuates Aß1-42-induced neurotoxicity in vitro.
Neurosci Lett
; 595: 63-8, 2015 May 19.
Article
en En
| MEDLINE
| ID: mdl-25849526
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 (Aß). 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 Aß1-42-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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Fragmentos de Péptidos
/
Péptidos beta-Amiloides
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Fármacos Neuroprotectores
/
Factor Neurotrófico Derivado del Encéfalo
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Neurosci Lett
Año:
2015
Tipo del documento:
Article
País de afiliación:
Corea del Sur
Pais de publicación:
Irlanda