The Protective Effect of Exercise in Neurodegenerative Diseases: The Potential Role of Extracellular Vesicles

Abstract

Physical activity has systemic effects on the body, affecting almost every organ. It is important not only for general health and wellbeing, but also in the prevention of diseases. The mechanisms behind the therapeutic effects of physical activity are not completely understood; however, studies indicate these benefits are not confined to simply managing energy balance and body weight. They also include systemic factors which are released into the circulation during exercise and which appear to underlie the myriad of benefits exercise can elicit. It was shown that along with a number of classical cytokines, active tissues also engage in inter-tissue communication via extracellular vesicles (EVs), specifically exosomes and other small EVs, which are able to deliver biomolecules to cells and alter their metabolism. Thus, EVs may play a role in the acute and systemic adaptations that take place during and after physical activity, and may be therapeutically useful in the treatment of a range of diseases, including metabolic disorders such as type 2 diabetes and obesity; and the focus of this review, neurological disorders such as Alzheimer’s disease.

Kinetics and Topology of DNA Associated with Circulating Extracellular Vesicles Released during Exercise

“…More recently, the analysis of the methylation profile of cfDNA shows that about 32% of cfDNA is derived from granulocytes, 30% from erythrocyte progenitors, 23% from monocytes and lymphocytes, 9% from endothelial cells, and only 6% from other cells including neurons and hepatocytes [ 11 ], while a sub-characterization for exercise released cfDNA has not been conducted yet. We and others found that next to muscle cells, platelets, endothelial cells, and leukocytes, significantly contribute to the pool of EVs released into plasma following physical exercise (reviewed in [ 47 , 62 , 63 , 64 ]). Like for cfDNA, the underlying signaling mechanisms are not fully understood, but an association with shear stress and the activation of coagulative processes are discussed [ 47 ].…”

Extracellular Vesicles and Exosomes: Insights From Exercise Science

“…Thus, the complete isolation of ELVs from other EVs becomes paramount. There is growing interest in the topic of SkMEV and proposed EV cargo in response to exercise ( Rome et al, 2019 ; Trovato et al, 2019 ; Vechetti, 2019 ; Murphy et al, 2020 ; Fuller et al, 2020 ). Given the challenge presented in tracking skeletal muscle-derived ELVs, whether miRNA cargo observed immediately following exercise is derived from the exercising muscle remains to be elucidated clearly.…”

Considerations for the Analysis of Small Extracellular Vesicles in Physical Exercise

“…The heterogeneity of EV populations and other bioactive particles in blood faces EV research with numerous challenges and, thus, confuses the determination of EVs released into the circulation upon physical exercise (ExerVs). The modalities of ExerV-release, the putative role in adaptation signaling as well as prospective therapeutic and diagnostic applications were recently highlighted and comprehensively summarized (e.g., Trovato et al, 2019 ; Fuller et al, 2020 ; Vechetti et al, 2020 ). Here, we supplement this body of literature with a compilation of the most relevant technical limitations regarding ExerV isolation and characterization, focusing on sEVs.…”