Figure 9.

Schematic diagram of consistent exercise in PD mice promoting the synthesis of FNDC5 in the muscle and its release into the blood. FNDC5 was also u-regulated in the brain, resulting in a protective effect on the hippocampus. Direct effects: FNDC5 activated integrin αV and β5 receptors on hippocampal neurons and promoted the activation of the CREB-mediated BDNF pathway. Indirect effects: FNDC5 promoted the interaction between the integrin receptors on the hippocampal neurons and the CD90 on the dopaminergic neurons to maintain the dopaminergic synaptic connection from the substantia nigra to the hippocampus.