PPARGC1A and Alzheimer disease: For example, exercise promotes muscle to secret fibronectin type III domain-containing protein 5 (FNDC5)/irisin, a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) dependent myokine, which promotes synaptic plasticity, reduces oxidative stress and ameliorates neuroinflammation in AD rodent models [16, 19, 28], proposing a connection between muscle and brain.