Fig. 3

Exercise modulates neuroinflammatory responses to ameliorate AD. First, exercise suppresses chronic inflammation in the body through reducing circulating levels of pro-inflammatory factors and immune cells. Second, exercise restores the permeability and integrity of the BBB by repairing damaged endothelial cells and tight junctions, ultimately preventing inflammatory factors and immune cells from entering the brain. Third, exercise inhibits the pro-inflammatory M1 phenotype and stimulates the anti-inflammatory M2 phenotype to increase the levels of anti-inflammatory factors in the brain, thereby restoring homeostasis. Finally, exercise triggers adult hippocampal neurogenesis (AHN) by inducing the expression of BDNF in the brain and muscle, thus leading to the continuous formation of new neurons, astrocytes, and oligodendrocytes. These new cells can replace the corresponding senescent and damaged cells, thus remodeling the high-loading state caused by neuroinflammation. Therefore, exercise inhibits the neuroinflammatory response through four effects and ultimately delays the pathological process of AD and alleviates symptoms