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

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2182 ◽  
Author(s):  
Oliver K Fuller ◽  
Martin Whitham ◽  
Suresh Mathivanan ◽  
Mark A Febbraio

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.

2021 ◽  
Author(s):  
Beate Vestad ◽  
Tuula Anneli Nyman ◽  
Malene Hove-Skovsgaard ◽  
Maria Stensland ◽  
Hedda Hoel ◽  
...  

Abstract Background: HIV and type 2 diabetes (T2D) are both associated with gut microbiota alterations, low-grade endotoxemia and increased cardiovascular risk. We investigated the potential role of plasma extracellular vesicles (EVs) in relation to these processes. Materials and methods: Plasma EVs were isolated by size exclusion chromatography in fasting individuals with HIV and T2D (n=16), T2D only (n=14), HIV only (n=20) or healthy controls (n=19), and characterized by transmission electron microscopy, western blot, nanoparticle tracking analysis and quantitative proteomics. The findings were compared to gut microbiota alterations, lipopolysaccharide levels and cardiovascular risk profile. Results: Individuals with concomitant HIV and T2D had higher plasma EV concentration, which correlated closely with plasma lipopolysaccharides, triglycerides and Framingham score, but not with gut microbiota alterations. Proteomic analyses identified 558 human proteins, largely related to cardiometabolic disease genes and upstream regulation of inflammatory pathways, including IL-6 and IL-1β, as well as 30 bacterial proteins, mostly from lipopolysaccharide-producing Proteobacteria. Conclusions: Our study supports that EVs are related to microbial translocation processes in individuals with HIV and T2D. Their proteomic content suggests a contributing role in low-grade inflammation and cardiovascular risk development. The present approach for exploring gut-host crosstalk can potentially identify novel diagnostic biomarkers and therapeutic targets.


Author(s):  
Nguyen Thu Huyen ◽  
Duong Minh Chau ◽  
Do Thi Xuan Phuong ◽  
Nguyen Thanh Liem ◽  
Than Thi Trang Uyen

Extracellular vesicles (EVs) are emerging as a potential candidate for disease treatment due to their bioactive cargoes. Recently, mesenchymal stem cells (MSC)-derived EVs have shown their capacity to replace parental cells as their similar functions to MSCs. The therapeutic effects of EVs depend on their cargo, such as DNA, miRNA, proteins, and lipids. In this study, we expanded umbilical cord-derived MSCs (UCMSCs) for EV release. Additionally, we evaluated the expression level of several microRNAs in three EV populations, including apoptotic bodies (AB), microvesicles (MV), and exosomes (EX). Results showed that UCMSCs released three EV types: AB, MV, and EX into culture media. The three EV populations were different in morphology and size. Three EVs were detected to carry microRNAs, such as hsa-miR-320, hsa-miR-181b, and hsa-miR-140. Among these microRNAs, hsa-miR-140 expressed with the greatest level, followed by hsa-miR-181b and hsa-miR-320. The results of this study provide more knowledge about UCMSC-derived EV miRNAs in addition to reveal the potential role of UCMSC-EVs associated with detected miRNAs.


2019 ◽  
Vol 8 (7) ◽  
pp. 322-326
Author(s):  
Gemma Fromage

Obesity has been defined as abnormal or excessive fat accumulation that may impair health. Obesity is associated with multiple comorbidities, affecting mechanical systems within the body as well as metabolic and mental health. If a person is overweight or obese, a loss of 5–10% of total body weight can have a number of health advantages. In the UK, there are three medications approved by the European Medicines Agency (EMA) for weight loss: orlistat, liraglutide and naltrexone in combination with bupropion. Liraglutide has the proprietary name Saxenda (Novo Nordisk). It may be prescribed for individuals with a body mass index (BMI) of 30 kg/m2 or more or people with a BMI of 27 kg/m2 who have another weight-related illness, such as high blood pressure, type 2 diabetes or dyslipidaemia. As with many weight-management programmes, liraglutide works in conjunction with a reduced-calorie diet and increased physical activity.


2020 ◽  
Vol 21 (18) ◽  
pp. 6765 ◽  
Author(s):  
Katherine E. Odegaard ◽  
Subhash Chand ◽  
Sydney Wheeler ◽  
Sneham Tiwari ◽  
Adrian Flores ◽  
...  

Extracellular vesicles (EVs) are a broad, heterogeneous class of membranous lipid-bilayer vesicles that facilitate intercellular communication throughout the body. As important carriers of various types of cargo, including proteins, lipids, DNA fragments, and a variety of small noncoding RNAs, including miRNAs, mRNAs, and siRNAs, EVs may play an important role in the development of addiction and other neurological pathologies, particularly those related to HIV. In this review, we summarize the findings of EV studies in the context of methamphetamine (METH), cocaine, nicotine, opioid, and alcohol use disorders, highlighting important EV cargoes that may contribute to addiction. Additionally, as HIV and substance abuse are often comorbid, we discuss the potential role of EVs in the intersection of substance abuse and HIV. Taken together, the studies presented in this comprehensive review shed light on the potential role of EVs in the exacerbation of substance use and HIV. As a subject of growing interest, EVs may continue to provide information about mechanisms and pathogenesis in substance use disorders and CNS pathologies, perhaps allowing for exploration into potential therapeutic options.


2010 ◽  
Vol 31 (3) ◽  
pp. 343-363 ◽  
Author(s):  
Oliver C. Richards ◽  
Summer M. Raines ◽  
Alan D. Attie

The pathogenesis of type 2 diabetes is intimately intertwined with the vasculature. Insulin must efficiently enter the bloodstream from pancreatic β-cells, circulate throughout the body, and efficiently exit the bloodstream to reach target tissues and mediate its effects. Defects in the vasculature of pancreatic islets can lead to diabetic phenotypes. Similarly, insulin resistance is accompanied by defects in the vasculature of skeletal muscle, which ultimately reduce the ability of insulin and nutrients to reach myocytes. An underappreciated participant in these processes is the vascular pericyte. Pericytes, the smooth muscle-like cells lining the outsides of blood vessels throughout the body, have not been directly implicated in insulin secretion or peripheral insulin delivery. Here, we review the role of the vasculature in insulin secretion, islet function, and peripheral insulin delivery, and highlight a potential role for the vascular pericyte in these processes.


Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 667
Author(s):  
Gabriella Racchetti ◽  
Jacopo Meldolesi

Mesenchymal stem cells (MSCs), the cells distributed in the stromas of the body, are known for various properties including replication, the potential of various differentiations, the immune-related processes including inflammation. About two decades ago, these cells were shown to play relevant roles in the therapy of numerous diseases, dependent on their immune regulation and their release of cytokines and growth factors, with ensuing activation of favorable enzymes and processes. Such discovery induced great increase of their investigation. Soon thereafter, however, it became clear that therapeutic actions of MSCs are risky, accompanied by serious drawbacks and defects. MSC therapy has been therefore reduced to a few diseases, replaced for the others by their extracellular vesicles, the MSC-EVs. The latter vesicles recapitulate most therapeutic actions of MSCs, with equal or even better efficacies and without the serious drawbacks of the parent cells. In addition, MSC-EVs are characterized by many advantages, among which are their heterogeneities dependent on the stromas of origin, the alleviation of cell aging, the regulation of immune responses and inflammation. Here we illustrate the MSC-EV therapeutic effects, largely mediated by specific miRNAs, covering various diseases and pathological processes occurring in the bones, heart and vessels, kidney, and brain. MSC-EVs operate also on the development of cancers and on COVID-19, where they alleviate the organ lesions induced by the virus. Therapy by MSC-EVs can be improved by combination of their innate potential to engineering processes inducing precise targeting and transfer of drugs. The unique properties of MSC-EVs explain their intense studies, carried out with extraordinary success. Although not yet developed to clinical practice, the perspectives for proximal future are encouraging.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 767
Author(s):  
Courtney Davis ◽  
Sean I. Savitz ◽  
Nikunj Satani

Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.


Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
A. L. Cunningham ◽  
J. W. Stephens ◽  
D. A. Harris

AbstractA strong and expanding evidence base supports the influence of gut microbiota in human metabolism. Altered glucose homeostasis is associated with altered gut microbiota, and is clearly associated with the development of type 2 diabetes mellitus (T2DM) and associated complications. Understanding the causal association between gut microbiota and metabolic risk has the potential role of identifying susceptible individuals to allow early targeted intervention.


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