Fig. 4From: Recent advances on the molecular mechanisms of exercise-induced improvements of cognitive dysfunctionExercise can improve the energy metabolism of the brain, which is beneficial to cognitive function. Insulin resistance: exercise reduces insulin resistance in the brain, allowing more insulin to reach the brain through the blood–brain barrier. Activation of the PI3K/Akt pathway can lead to activation of mTOR and CRMP-2 as well as inhibition of GSK3β, resulting in ①decreased deposition of Tau and Aβ proteins, neurofibrillary tangles (NFTs), and aggregation of mHtt; ② activation of hippocampal autophagy and clearance of NFTs; and ③ improved synaptic activity of dopaminergic neurons. Glucose metabolism: exercise increases the amount of GLUTs that can remove more glucose to the cytoplasm. Glucose undergoes glycolysis and the tricarboxylic acid cycle to provide more ATP to brain tissue. Microglia: TREM2, by binding to DAP10/12, promotes Syk phosphorylation and regulates metabolic processes, including energy generation, calcium mobilization and brain metabolismBack to article page