The Power of Exercise: Unlocking the Biological Mysteries of Peripheral-Central Crosstalk in Parkinson’s Disease
Jingwen Li, Tingting Liu, Meiyan Xian, Ke Zhou, Jianshe Wei
Abstract
This review recent research on the mechanisms through which exercise improves Parkinson’s disease (PD) by examining the interactions between peripheral signals and central nervous system pathways. Exercise stimulates the secretion of cytokines via multiple axes, including the gut-brain, muscle-brain, liver-brain, adipose-brain, and bone-brain axes. These cytokines are capable of crossing the blood–brain barrier, thereby contributing to the improvement of PD symptoms. Additionally, axes such as the heart-brain, lung-brain, spleen-brain, brain-gut-muscle, and brain-gut-bone axes may also mediate the beneficial effects of exercise on PD, though further research is required to clarify their roles. • Previous studies investigating the effects of exercise on PD have primarily focused on the adaptive changes in the structure and function of the central nervous system. • Exercise can influence PD through the interactions between peripheral signals and central systems. • Exercise can improve PD by secreting relevant cytokines through the gut-brain axis, muscle-brain axis, liver-brain axis, adipose-brain axis, and bone-brain axis. • The heart-brain axis, lung-brain axis, spleen-brain axis, brain-gut-muscle axis, and brain-gut-bone axis may also play a role in improving PD through exercise, and further research is needed. Exercise is a widely recognized non-pharmacological treatment for Parkinson’s Disease (PD). The bidirectional regulation between the brain and peripheral organs has emerged as a promising area of research, with the mechanisms by which exercise impacts PD closely linked to the interplay between peripheral signals and the central nervous system. This review aims to summarize the mechanisms by which exercise influences peripheral-central crosstalk to improve PD, discuss the molecular processes mediating these interactions, elucidate the pathways through which exercise may modulate PD pathophysiology, and identify directions for future research. This review examines how exercise-induced cytokine release promotes neuroprotection in PD. It discusses how exercise can stimulate cytokine secretion through various pathways, including the gut-brain, muscle-brain, liver-brain, adipose-brain, and bone-brain axes, thereby alleviating PD symptoms. Additionally, the potential contributions of the heart-brain, lung-brain, and spleen-brain axes, as well as multi-axis crosstalk—such as the brain-gut-muscle and brain-gut-bone axes—are explored in the context of exercise therapy. The study highlights the need for further research into peripheral-central crosstalk and outlines future directions to address challenges in clinical PD therapy.