FGF21 Attenuates Neurodegeneration though Modulating Neuroinflammation and Oxidant-stress

Abstract

Background It is reported that FGF21 can repair nerve injury, but the specific mechanism is less studied. The present study was designed to investigate the effects of FGF21 on neurodegeneration and possible mechanisms of the aging and diabetic mice, which were susceptible to Alzheimer's disease (AD). Methods The diabetic mice and aging mice were used to study the effects of FGF21 on neurodegeneration and possible mechanisms. These mice were administrated with PBS, FGF21 or metformin once daily for 4 or 6 months. Then the mechanism was verified in SH-SY5Y cells. The relative gene expressions for neurodegeneration were assessed by Quantitative Real Time-PCR, Western blot and others. Results FGF21 inhibited the loss of nerve cells and intracellular edema around hippocampus in diabetic mice and aging mice. In vivo results revealed that administration of FGF21 led to suppress the aggregation of Tau and β-Amyloid 1-42 , which resulted in apoptosis in nerve cells. Meanwhile, FGF21 significantly reduced the expression of NF-κB, IL6 and IL8 (p<0.05) and enhanced anti-oxidant enzymes (p<0.05) in diabetic mice. In addition, the phosphorylation of AKT and AMPKα was increased by FGF21 treated in diabetic mice, which were considered as anti-inflammation and anti-oxidant stress pathway. The relative gene expressions of neurodegeneration were also demonstrated in aging mice, which showed similar trends with diabetic mice. In vitro experiment showed that the aggregation of Tau and β-Amyloid 1-42 was increased by LPS in SH-SY5Y cells, and FGF21 inhibited the aggregation. Conclusion As shown above, FGF21 attenuated neurodegeneration by reducing neuroinflammation and oxidant stress though regulating the NF-κB pathway and AMPKα/AKT pathway, which enhanced the protective effect on mitochondria in nerve cells. Key words : FGF21, diabetes, neurodegeneration, inflammation, oxidant stress.

MiR-146b-5p/TRAF6 axis is essential for Ginkgo biloba L. extract GBE to attenuate LPS-induced neuroinflammation

“…Neuroinflammation is a protective mechanism in which inflammatory mediators repair damaged neurons and glial cells during acute neuroinflammation (Cobourne-Duval et al, 2018;von Bernhardi et al, 2015;Yang et al, 2020). However, chronic neuroinflammation often leads to neuronal damage and eventual degeneration (Kempuraj et al, 2016;Cobourne-Duval et al, 2018;Kang et al, 2020). For many years, neuroinflammation has been considered a vital driver of many brain diseases (Bidstrup, 1972;Heneka et al, 2015), such as the neurodegenerative Alzheimer's disease (AD).…”