Figure 2.

Exercise-induced neuroprotection through circulating myokines. Exercise induces increased peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α) expression and supports induction of different myokines such as FDN5/Irisin, cathepsin B (CTSB), fibroblast growth factor 21 (FGF21), and lactate. FDN5/Irisin induces brain-derived neurotrophic factor (BDNF) expression in the brain through indirect inhibition of histone deacetylase 1(HDAC-1). Several of these factors increase signalling of BDNF and its receptor Tropomyosin receptor kinase B (TRKB), or reduce excessive reactive oxygen species (ROS) production. In addition, lactate increases the expression of the vascular endothelial growth factor (VEGF) and of the synaptic plasticity genes: Arc, c-FOS and ZIF268.