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

• Published in: Neurotoxicity research Vol. 34; no. 3; pp. 574 - 583
• Main Authors: Amiri, Mona, Braidy, Nady, Aminzadeh, Malihe
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2018
• Subjects: Biomedical and Life Sciences; Biomedicine; Cell Biology; Neurobiology; Neurochemistry; Neurology; Neurosciences; Original Article; Pharmacology/Toxicology; Amyloid beta 42; Oxidative stress; Neuroinflammation; Neuroblastoma; Alzheimer’s disease; FGF21
• ISSN: 1029-8428; 1476-3524
• DOI: 10.1007/s12640-018-9914-2

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 Aβ 1–42 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 Aβ 1–42 toxicity in SH-SY5Y neuroblastoma cells. Our data shows that FGF21 significantly decreased Aβ 1− 42-induced toxic effects and repressed oxidative stress and apoptosis in cells exposed to Aβ 1–42 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 Aβ 1–42 -induced cellular inflammation and apoptotic death in the SH-SY5Y neuroblastoma cells.