Fig. 4
From: Exercise mimetics: a novel strategy to combat neuroinflammation and Alzheimer’s disease
Exercise mimetics for improvement neuroinflammation and AD. The neuroprotective effects of exercise are regulated by a variety of molecular factors that can be activated in a way similar to exercise through the administration of exercise mimetics. These mimetics have been shown to be effective in reducing neuroinflammation and managing AD pathology, making them a valuable alternative for patients who are unable to follow regular physical activity. Exercise benefits the brain through communication between peripheral organs and the brain, such as muscle–brain crosstalk, liver–brain crosstalk, and gut–brain crosstalk. Exercise increases the secretion of FNDC5/irisin from muscles, which can reduce oxidative stress and alleviate neuroinflammation in AD. The liver also generates important factors such as Gpld1 and SAM that are crucial for metabolism and neuroinflammation and can cross the BBB to affect brain function in various AD models. Progress in understanding the molecular mechanisms underlying these interactions endows patients to better utilize the power of exercise mimetics to improve health outcomes. AD, Alzheimer’s disease; BBB, blood–brain barrier; FNDC5, fibronectin type III domain-containing protein 5; Gpld1, glycosylphosphatidylinositol-specific phospholipase D1; SAM, S-adenosylmethionine