Fig. 3

Exercise for neuroinflammation and AD. Physical exercise can exert multiple positive effects on the brain of AD, such as enhancing cerebral blood flow, neurogenesis, synaptic plasticity, neurotrophic factors, antioxidant defense, and cognitive function. Exercise can inhibit the formation and deposition of Aβ and abnormal phosphorylation of Tau, partly by affecting α- and γ-secretase activity, BDNF production, and BACE1 function. More importantly, physical exercise can modulate neuroinflammation by directly and indirectly mediating the immune response of the CNS. Physical exercise can impact the activation state and phenotype of microglia and astrocytes in AD, resulting in the shift of the polarization of microglia and astrocytes from a pro-inflammatory (M1 or A1) to an anti-inflammatory (M2 or A2) pattern. This immune action results in reduced production of pro-inflammatory cytokines and enhanced production of anti-inflammatory molecules. Furthermore, physical exercise can suppress the activation of inflammasomes, such as NLRP3, which in turn decreases the production of IL-1β and caspase-1. Additionally, physical exercise can strengthen the thigh connection of the BBB, which can prevent the infiltration of peripheral immune cells and inflammatory molecules into the brain. AD, Alzheimer’s disease; Aβ, amyloid beta; BACE1, beta site APP cleaving enzyme 1