FGF21 Attenuates Neurodegeneration though Reducing Neuroinflammation and Oxidant-stress

Abstract Background It is reported that FGF21 can repair the nerve injury, but the specific mechanism is less studied. The present study was designed to investigate the effects and possible mechanisms of FGF21 on neurodegeneration of the aging in 20 month old C57BL/6 mice and the diabetes in C57BL/ksj -db/db mice which were susceptible to Alzheimer’s disease (AD). Methods The db/db mice and aging mice were used to verify the effects and possible mechanisms of FGF21 on neurodegeneration. These mice was processed with PBS, FGF21 or metformin once daily for several months. The related indicators of neurodegeneration were assessed by Quantitative Real Time-PCR, western blot and others.Results There were loss of nerve cells and intracellular edema around hippocampus in db/db mice and aging mice which were inhibited by FGF21. In vivo investigation revealed that the procession of FGF21 led to suppress the aggregation of Tau and β-Amyloid1-42 which led to apoptosis in nerve cells. Meanwhile, FGF21 significantly decreased the expression of NF-κB, IL6 and IL8 (p<0.05) and increased anti-oxidant enzymes (p<0.05) in db/db mice. In addition, the phosphorylation of AKT and AMPKα were increased by FGF21 in db/db mice, which were considered as anti-inflammation and anti-oxidant stress pathway. The related indicators of neurodegeneration were also exhibited in aging mice which showed similar trends. The vitro experiment showed that the aggregation of Tau and β-Amyloid1-42 were increased by LPS, and hyperaggregation of Tau and β-Amyloid1-42 were inhibited by FGF21 in SHSY-5Y cells. Conclusion It was concluded that FGF21 attenuated neurodegeneration by reducing neuroinflammation and oxidant stress though regulating the NF-κB pathway and AMPK pathway which enhanced the protective effect of mitochondria on nerve cells.