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Protective Effects of Fibroblast Growth Factor 21 Against Amyloid-Beta1–42-Induced Toxicity in SH-SY5Y Cells

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of cholinergic neurons. Amyloid beta is a misfolded protein that represents one of the key pathological hallmarks of AD. Numerous studies have shown that Aβ1–42 induces oxidative damage, neuroinflammation, and apoptosis, leading to cognitive decline in AD. Recently, fibroblast growth factor 21 (FGF21) has been suggested to be a potential regulator of oxidative stress in mammalian cells. FGF21 has been shown to improve insulin sensitivity, reduce hyperglycemia, increase adipose tissue glucose uptake and lipolysis, and decrease body fat and weight loss by enhancing energy expenditure. In this study, we investigated the effect of FGF21 Aβ1–42 toxicity in SH-SY5Y neuroblastoma cells. Our data shows that FGF21 significantly decreased Aβ1−42-induced toxic effects and repressed oxidative stress and apoptosis in cells exposed to Aβ1–42 peptide. Our investigation also confirmed that FGF21 pretreatment favorably affects HSP90/TLR4/NF-κB signaling pathway. Therefore, FGF21 represents a viable therapeutic strategy to abrogate Aβ1–42-induced cellular inflammation and apoptotic death in the SH-SY5Y neuroblastoma cells.

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Funding

This study was part of a M.Sc. thesis project that was approved and financially supported by Iran University of Medical Sciences in 2016 (grant#94-04-30- 26938).

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Mona Amiri

  2. Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Barker Street, Randwick, Sydney, NSW, 2031, Australia

    Nady Braidy

  3. Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran

    Malihe Aminzadeh

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  1. Mona Amiri
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  2. Nady Braidy
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  3. Malihe Aminzadeh
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Correspondence to Mona Amiri or Nady Braidy.

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Amiri, M., Braidy, N. & Aminzadeh, M. Protective Effects of Fibroblast Growth Factor 21 Against Amyloid-Beta1–42-Induced Toxicity in SH-SY5Y Cells. Neurotox Res 34, 574–583 (2018). https://doi.org/10.1007/s12640-018-9914-2

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