scholarly journals Extracellular Vesicles in Multiple Sclerosis: Role in the Pathogenesis and Potential Usefulness as Biomarkers and Therapeutic Tools

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1733
Author(s):  
Marianna D’Anca ◽  
Chiara Fenoglio ◽  
Francesca Romana Buccellato ◽  
Caterina Visconte ◽  
Daniela Galimberti ◽  
...  

Although extracellular vesicles (EVs) were initially relegated to a waste disposal role, nowadays, they have gained multiple fundamental functions working as messengers in intercellular communication as well as exerting active roles in physiological and pathological processes. Accumulating evidence proves the involvement of EVs in many diseases, including those of the central nervous system (CNS), such as multiple sclerosis (MS). Indeed, these membrane-bound particles, produced in any type of cell, carry and release a vast range of bioactive molecules (nucleic acids, proteins, and lipids), conferring genotypic and phenotypic changes to the recipient cell. This means that not only EVs per se but their content, especially, could reveal new candidate disease biomarkers and/or therapeutic agents. This review is intended to provide an overview regarding current knowledge about EVs’ involvement in MS, analyzing the potential versatility of EVs as a new therapeutic tool and source of biomarkers.

2020 ◽  
Vol 21 (20) ◽  
pp. 7688 ◽  
Author(s):  
Ancuta Jurj ◽  
Cecilia Pop-Bica ◽  
Ondrej Slaby ◽  
Cristina D. Ştefan ◽  
William C. Cho ◽  
...  

Communications among cells can be achieved either via direct interactions or via secretion of soluble factors. The emergence of extracellular vesicles (EVs) as entities that play key roles in cell-to-cell communication offer opportunities in exploring their features for use in therapeutics; i.e., management and treatment of various pathologies, such as those used for cancer. The potential use of EVs as therapeutic agents is attributed not only for their cell membrane-bound components, but also for their cargos, mostly bioactive molecules, wherein the former regulate interactions with a recipient cell while the latter trigger cellular functions/molecular mechanisms of a recipient cell. In this article, we highlight the involvement of EVs in hallmarks of a cancer cell, particularly focusing on those molecular processes that are influenced by EV cargos. Moreover, we explored the roles of RNA species and proteins carried by EVs in eliciting drug resistance phenotypes. Interestingly, engineered EVs have been investigated and proposed as therapeutic agents in various in vivo and in vitro studies, as well as in several clinical trials.


2021 ◽  
Vol 22 (3) ◽  
pp. 1365
Author(s):  
Santra Brenna ◽  
Christoph Krisp ◽  
Hermann Clemens Altmeppen ◽  
Tim Magnus ◽  
Berta Puig

Extracellular vesicles (EVs) are double membrane structures released by presumably all cell types that transport and deliver lipids, proteins, and genetic material to near or distant recipient cells, thereby affecting their phenotype. The basic knowledge of their functions in healthy and diseased brain is still murky and many questions about their biology are unsolved. In neurological diseases, EVs are regarded as attractive biomarkers and as therapeutic tools due to their ability to cross the blood–brain barrier (BBB). EVs have been successfully isolated from conditioned media of primary brain cells and cerebrospinal fluid (CSF), but protocols allowing for the direct study of pathophysiological events mediated or influenced by EVs isolated from brain have only recently been published. This review aims to give a brief overview of the current knowledge of EVs’ functions in the central nervous system (CNS) and the current protocols to isolate brain-derived EVs (BDEVs) used in different publications. By comparing the proteomic analysis of some of these publications, we also assess the influence of the isolation method on the protein content of BDEVs.


2021 ◽  
Vol 22 (4) ◽  
pp. 2213
Author(s):  
Natalia Diaz-Garrido ◽  
Cecilia Cordero ◽  
Yenifer Olivo-Martinez ◽  
Josefa Badia ◽  
Laura Baldomà

Communication between cells is crucial to preserve body homeostasis and health. Tightly controlled intercellular dialog is particularly relevant in the gut, where cells of the intestinal mucosa are constantly exposed to millions of microbes that have great impact on intestinal homeostasis by controlling barrier and immune functions. Recent knowledge involves extracellular vesicles (EVs) as mediators of such communication by transferring messenger bioactive molecules including proteins, lipids, and miRNAs between cells and tissues. The specific functions of EVs principally depend on the internal cargo, which upon delivery to target cells trigger signal events that modulate cellular functions. The vesicular cargo is greatly influenced by genetic, pathological, and environmental factors. This finding provides the basis for investigating potential clinical applications of EVs as therapeutic targets or diagnostic biomarkers. Here, we review current knowledge on the biogenesis and cargo composition of EVs in general terms. We then focus the attention to EVs released by cells of the intestinal mucosa and their impact on intestinal homeostasis in health and disease. We specifically highlight their role on epithelial barrier integrity, wound healing of epithelial cells, immunity, and microbiota shaping. Microbiota-derived EVs are not reviewed here.


Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1327 ◽  
Author(s):  
Loredana Leggio ◽  
Greta Paternò ◽  
Silvia Vivarelli ◽  
Francesca L’Episcopo ◽  
Cataldo Tirolo ◽  
...  

Extracellular vesicles (EVs) are naturally occurring membranous structures secreted by normal and diseased cells, and carrying a wide range of bioactive molecules. In the central nervous system (CNS), EVs are important in both homeostasis and pathology. Through receptor–ligand interactions, direct fusion, or endocytosis, EVs interact with their target cells. Accumulating evidence indicates that EVs play crucial roles in the pathogenesis of many neurodegenerative disorders (NDs), including Parkinson′s disease (PD). PD is the second most common ND, characterized by the progressive loss of dopaminergic (DAergic) neurons within the Substantia Nigra pars compacta (SNpc). In PD, EVs are secreted by both neurons and glial cells, with either beneficial or detrimental effects, via a complex program of cell-to-cell communication. The functions of EVs in PD range from their etiopathogenetic relevance to their use as diagnostic tools and innovative carriers of therapeutics. Because they can cross the blood–brain barrier, EVs can be engineered to deliver bioactive molecules (e.g., small interfering RNAs, catalase) within the CNS. This review summarizes the latest findings regarding the role played by EVs in PD etiology, diagnosis, prognosis, and therapy, with a particular focus on their use as novel PD nanotherapeutics.


2019 ◽  
Vol 20 (8) ◽  
pp. 1848 ◽  
Author(s):  
Stefania Raimondo ◽  
Gianluca Giavaresi ◽  
Aurelio Lorico ◽  
Riccardo Alessandro

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)—specialized membrane-bound nanocarriers for intercellular communication—suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, we will discuss the current developments in the field of animal and plant-derived EVs toward their potential use for delivery of therapeutic agents in different pathological conditions, with a special focus on cancer.


2020 ◽  
Vol 217 (4) ◽  
Author(s):  
Caterina P. Profaci ◽  
Roeben N. Munji ◽  
Robert S. Pulido ◽  
Richard Daneman

The blood vessels vascularizing the central nervous system exhibit a series of distinct properties that tightly control the movement of ions, molecules, and cells between the blood and the parenchyma. This “blood–brain barrier” is initiated during angiogenesis via signals from the surrounding neural environment, and its integrity remains vital for homeostasis and neural protection throughout life. Blood–brain barrier dysfunction contributes to pathology in a range of neurological conditions including multiple sclerosis, stroke, and epilepsy, and has also been implicated in neurodegenerative diseases such as Alzheimer’s disease. This review will discuss current knowledge and key unanswered questions regarding the blood–brain barrier in health and disease.


2021 ◽  
Vol 12 ◽  
Author(s):  
Gianmarco Bellucci ◽  
Virginia Rinaldi ◽  
Maria Chiara Buscarinu ◽  
Roberta Reniè ◽  
Rachele Bigi ◽  
...  

Current knowledge on Multiple Sclerosis (MS) etiopathogenesis encompasses complex interactions between the host’s genetic background and several environmental factors that result in dysimmunity against the central nervous system. An old-aged association exists between MS and viral infections, capable of triggering and sustaining neuroinflammation through direct and indirect mechanisms. The novel Coronavirus, SARS-CoV-2, has a remarkable, and still not fully understood, impact on the immune system: the occurrence and severity of both acute COVID-19 and post-infectious chronic illness (long COVID-19) largely depends on the host’s response to the infection, that echoes several aspects of MS pathobiology. Furthermore, other MS-associated viruses, such as the Epstein-Barr Virus (EBV) and Human Endogenous Retroviruses (HERVs), may enhance a mechanistic interplay with the novel Coronavirus, with the potential to interfere in MS natural history. Studies on COVID-19 in people with MS have helped clinicians in adjusting therapeutic strategies during the pandemic; similar efforts are being made for SARS-CoV-2 vaccination campaigns. In this Review, we look over 18 months of SARS-CoV-2 pandemic from the perspective of MS: we dissect neuroinflammatory and demyelinating mechanisms associated with COVID-19, summarize pathophysiological crossroads between MS and SARS-CoV-2 infection, and discuss present evidence on COVID-19 and its vaccination in people with MS.


US Neurology ◽  
2017 ◽  
Vol 13 (02) ◽  
pp. 90
Author(s):  
Meena R Kannan ◽  
Vijayshree Yadav ◽  
◽  

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system and the most common non-traumatic cause of disability in young adults. Recent research shows that vascular disease risk factors (VDRFs) such as obesity, smoking, hyperlipidemia, hypertension, type II diabetes mellitus, and metabolic syndrome, can influence MS on its onset, disease activity, progression, and resultant disability. This review evaluates the current knowledge on the role of VDRFs on outcomes among people with MS (PwMS) and shows that while VDRF prevalence may or may not be higher among PwMS compared with the general population, its presence can influence MS in myriad ways. Management of VDRFs through early detection and treatment may be a promising approach to improving outcomes in PwMS.


2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Qian Jin ◽  
Peipei Wu ◽  
Xinru Zhou ◽  
Hui Qian ◽  
Wenrong Xu

Exosomes are small extracellular vesicles (EVs) secreted by almost all cells, which have been recognized as a novel platform for intercellular communication in the central nervous system (CNS). Exosomes are capable of transferring proteins, nucleic acids, lipids, and metabolites between neurons and glial cells, contributing to CNS development and maintenance of homeostasis. Evidence shows that exosomes originating from CNS cells act as suppressors or promoters in the initiation and progression of neurological disorders. Moreover, these exosomes have been shown to transfer molecules associated with diseases through the blood-brain barrier (BBB) and thus can be detected in blood. This unique feature enables exosomes to act as potential diagnostic biomarkers for neurological disorders. In addition, a substantial number of researches have indicated that exosomes derived from mesenchymal stem cells (MSCs) have repair effects on neurological disorders. Herein, we briefly introduce the roles of exosomes under physiological and pathological conditions. In particular, novel roles of exosomes as potential diagnostic biomarkers and therapeutic tools for neurological disorders are highlighted.


Proteomes ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 21 ◽  
Author(s):  
Magdalena Surman ◽  
Ewa Stępień ◽  
Małgorzata Przybyło

Malignant melanoma is one of the most aggressive types of cancer, and its incidence is increasing rapidly each year. Despite the extensive research into improved diagnostic and treatment methods, early detection and disease constraint still present significant challenges. As successful isolation protocols have been developed, extracellular vesicles (EVs) have become the subject of extensive investigation in terms of their role in cancer progression and as a possible source of disease biomarkers. Besides functional studies, quantitative and qualitative proteomics have recently emerged as promising tools for the advancement of melanoma biomarkers. Nevertheless, the amount of data concerning the proteome of melanoma-derived EVs is still very limited. In this review we cover the current knowledge on protein content of melanoma-derived EVs, with a focus on their potential role in the development and progression of melanomas.


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