FNDC5/irisin expression stimulates neuroprotective pathways in hippocampal neurons and associates with Alzheimer’s disease pathology

Background Irisin is an exercise-linked myokine produced by cleavage of the membrane precursor fibronectin type III domain-containing protein 5 (FNDC5) in skeletal muscle, brain, and other tissues. Recently, irisin has been identified as a key molecule for exercise-induced neuroprotection mouse models Alzheimer’s disease (AD). However, role FNDC5/irisin AD pathology not yet comprehensively explored. Here, we investigated potential mechanisms underlying induced AD. Method Primary rat hippocampal neuronal cultures were transduced with adenoviral vectors to express FNDC5 (AdFNDC5) or GFP (as control) exposed recombinant (25 nM) defined timepoints. Brain-derived neurotrophic factor (BDNF) levels measured ELISA; extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation was determined Western blotting; effects on amyloid-β oligomers (AβO)-induced reactive oxygen species (ROS) accumulation DCF fluorescence. Finally, analyzed RNA-seq data from human postmortem hippocampi within The Aging, Dementia Traumatic Brain Injury Study determine correlations between gene expression pathology. Result We found that stimulates BDNF accumulation, ERK (i.e. activation) prevents AβOs-induced ROS primary neurons. Analysis indicates reduced aging tau (assessed Braak neuropathological scale phospho-tau immunoreactivity), but amyloid humans. Conclusion These results indicate which signaling promotes support notion stimulation may be beneficial against neurodegeneration