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Neuropeptide VGF-Derived Peptide LQEQ-19 has Neuroprotective Effects in an In Vitro Model of Amyotrophic Lateral Sclerosis

  • Y. Noda
  • S. Motoyama
  • S. Nakamura
  • M. Shimazawa
  • H. HaraEmail author
Original Paper

Abstract

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease caused by the loss of upper and lower motor neurons resulting in muscle weakness and paralysis. Recently, VGF, a neuropeptide that is a precursor of bioactive polypeptides, was found to be decreased in ALS patients, and its inducer exerted protective effects in models of ALS. These findings suggested that VGF was involved in the pathology of ALS. Here, we investigated the neuroprotective effects of various VGF-derived peptides in an in vitro ALS model. We applied seven VGF-derived peptides (TLQP-21, AQEE-30, AQEE-11, LQEQ-19, QEEL-16, LENY-13, and HVLL-7) to the motor neuron-derived cell line, NSC-34, expressing SOD1G93A, which is one of the mutated proteins responsible for familial ALS. Nuclear staining revealed that AQEE-30 and LQEQ-19, which are derived from the C-terminal polypeptide of the VGF precursor protein, attenuated neuronal cell death. Furthermore, immunoblot analysis demonstrated that LQEQ-19 promoted the phosphorylation of Akt and extracellular signal-regulated kinase (ERK) 1/2, and inhibiting these mitogen-activated MAP kinases (MAPKs) with phosphoinositide 3-kinase or MEK/ERK inhibitors, eliminated the neuroprotective effects of LQEQ-19. In conclusion, these results suggest that VGF C-terminal peptides exert their neuroprotective effects via activation of MAPKs such as Akt and ERK1/2. Furthermore, these findings indicate that VGF-derived peptides have potential application in ALS therapy.

Keywords

VGF AQEE-30 LQEQ-19 Akt Extracellular signal-regulated kinase 

Notes

Compliance with Ethical Standards

Conflict of interest

The authors have declared that no competing interests exist.

Supplementary material

11064_2019_2725_MOESM1_ESM.docx (29 kb)
Supplementary material 1 (DOCX 29 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Y. Noda
    • 1
  • S. Motoyama
    • 1
  • S. Nakamura
    • 1
  • M. Shimazawa
    • 1
  • H. Hara
    • 1
    Email author
  1. 1.Molecular Pharmacology, Department of Biofunctional EvaluationGifu Pharmaceutical UniversityGifuJapan

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