Extracellular Vesicles as Pro- and Anti-inflammatory Mediators, Biomarkers and Potential Therapeutic Agents in Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease of the central nervous system (CNS) characterized by multiple demyelinating lesions in the spinal cord and brain. Neuronal disruption caused by myelin loss or demyelination, which may accompany axonal changes, leads to multiple neurological symptoms. They may transiently appear for weeks during periods of disease worsening (relapse) in relapsingremitting form of MS (RRMS). Although a number of genetic, metabolic and environmental factors influencing the development of MS have been identified, the precise mechanisms involved in the CNS tissue damage in MS are still poorly understood. Recent studies have revealed a significant role of circulating extracellular vesicles (EVs) in many diseases. EVs are known to serve as a cellular communication tool between two cell types either in close proximity or in different parts of the body. During the recent development in understanding of the pathogenesis of MS, studies have revealed the possible role of EVs in MS. Furthermore, circulating EVs can be used as a biomarker for monitoring disease progression and activity of MS, and they can also be therapeutic reagents or targets of therapy. In this review we overview and discuss in detail about generation of EVs and their diversified roles in MS.

L1CAM‐associated extracellular vesicles: A systematic review of nomenclature, sources, separation, and characterization

“…EVs have also been reported to cross bodily barriers such as the mammalian blood-brain barrier ( Alvarez-Erviti et al, 2011 ; Dickens et al, 2017 ; Pulliam, Sun, Mustapic, Chawla, & Kapogiannis, 2019 ; Russell et al, 2019 ). Due to the relative clinical inaccessibility of the brain, diseases and conditions of the central nervous system (CNS), including neurodegenerative diseases such as Alzheimer’s and Parkinson’s, present diagnostic, prognostic, and monitoring challenges for which EVs in biofluids are a potential solution ( Campbell & Mocchetti, 2021 ; Coleman & Hill, 2015 ; Manu, Hohjoh, & Yamamura, 2021 ; Thompson et al, 2016 ; Upadhya & Shetty, 2021 ; Vandendriessche, Bruggeman, Van Cauwenberghe, & Vandenbroucke, 2020 ) as a kind of ‘liquid biopsy’: if displaying markers of the cell of origin, EVs and their cargo of proteins, nucleic acids, and more can theoretically be traced back to the parent cells and can serve as indicators of cell and tissue health ( Pulliam et al, 2019 ; Shankar, Balaj, Stott, Nahed, & Carter, 2017 ; Vassileff, Cheng, & Hill, 2020 ). However, realizing the promise of EVs requires highly specific and abundant surface markers that can be used as molecular handles to separate target EVs from the high background of EVs from other cells in biofluids like blood ( Thompson et al, 2016 ).…”

Current and Future Biomarkers in Multiple Sclerosis

“…Exosomes can be used to communicate between cells and travel large distances in the body. Thus, they can be used to monitor MS disease progression and activity as well as therapeutic treatment [ 141 ]. Exosomes can be released from T cells to regulate antigen presenting cells via miRNAs contained within the exosome [ 142 ] and act as proinflammatory regulators in rheumatoid arthritis, Grave’s disease, and in MS [ 143 , 144 , 145 ].…”

“…Exosomes can be released from T cells to regulate antigen presenting cells via miRNAs contained within the exosome [ 142 ] and act as proinflammatory regulators in rheumatoid arthritis, Grave’s disease, and in MS [ 143 , 144 , 145 ]. EVs are found to be increased in the CSF and plasma of MS patients and have different molecular compositions compared to EVs from healthy individuals [ 141 ]. A study found that patients with RRMS had significantly altered miRNAs compared to controls, specifically an increase in miRNA let-7i in exosomes [ 146 ].…”

Berberine: A Promising Treatment for Neurodegenerative Diseases

“…Multiple sclerosis, characterized by multiple demyelinating lesions of the spinal cord and brain, has a progressive neurodegenerative pattern ( Manu et al, 2021 ; Zahid et al, 2021 ). Berberine has been reported as a potential drug for the treatment of multiple sclerosis.…”