Elsevier

Clinical Therapeutics

Volume 36, Issue 6, 1 June 2014, Pages 882-888
Clinical Therapeutics

Review Article
Exosomes in Neurologic and Psychiatric Disorders

https://doi.org/10.1016/j.clinthera.2014.05.005Get rights and content

Abstract

Purposes

The purposes of this review were to discuss the role of exosomes in neurologic and psychiatric diseases and to propose future therapeutic approaches.

Methods

PubMed was searched (2000–2014) using the terms exosomes, microvesicles, neurological disorders, psychiatric disorders, multivesicular bodies, Alzheimer’s disease, Parkinson’s disease, prion disease, multiple sclerosis, schizophrenia, glioblastoma multiforme, and flavonoids.

Findings

Many cells of the nervous system have been reported to release exosomes that could have an active role in the function, development, and diseases of the CNS, such as Alzheimer disease, Parkinson disease, prion diseases, multiple sclerosis, brain tumors, and schizophrenia. In all of these diseases, exosomes are involved in the spread of “toxic” proteins that are mutated or “misfolded” and serve as templates for the formation of disease-producing oligomers.

Implications

Exosomes’ simple structure and abilities to be incorporated into plasma membrane and to cross the blood–brain barrier allow for the opportunity to utilize them as delivery vehicles of drugs and genetic elements in the treatment of immune, psychiatric, and neurologic disorders. Flavonoids have emerged as unique, natural molecules with antioxidant and antiinflammatory properties. It would, therefore, be of interest to design flavonoid-containing exosomes.

Introduction

Exosomes are small membrane vesicles secreted by diverse cell types (eg, neurons, tumor cells, and kidney cells).1 They are secreted in the intercellular space but can be isolated from various biological fluids, such as plasma, urine, cerebrospinal fluid, epididymal fluid, amniotic fluid, malignant and pleural effusions of ascites, bronchoalveolar lavage fluid, synovial fluid, and breast milk, suggesting a role in the exchange of biological information across distant bodily compartments.2 Exosomes are either generated from the cell when multivesicular bodies (MVBs) fuse with the plasma membranes, or they are released directly from the plasma membrane.3 Exosomes secreted in bodily fluids contain a variety of proteins, lipids, noncoding RNAs, mRNAs, and microRNAs (miRNAs) that are delivered to the surrounding cells or are carried to distal sites.4, 5

The role that exosomes may play in the central nervous system (CNS) is the subject of active investigation.6 Many cells of the nervous system have been reported to release exosomes that may have an active role in the function, development, and diseases of the CNS.7 Interestingly, exosomes have been found to be associated with several proteins, such as amyloid precursor protein and α-synuclein, which appear to be involved in Alzheimer disease (AD) and Parkinson disease (PD), respectively.8 Recent findings have also implied an unexpected role of exosomes, and their mode of membrane exchange, in the transmission of a pathogen called the prion, which is involved in Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy (scrapie).9

Based on these findings, exosomes comprise a source of multiple markers that provide clinically useful information. The purposes of this review were to discuss the role of exosomes in neurologic and psychiatric diseases and to propose future therapeutic approaches.

Section snippets

Materials And Methods

PubMed was searched for relevant articles published from 2000 to 2014 using the terms exosomes, microvesicles, neurological disorders, psychiatric disorders, multivesicular bodies, Alzheimer’s disease, Parkinson’s disease, prion disease, multiple sclerosis, schizophrenia, glioblastoma multiforme, and flavonoids.

Results

The literature search identified 71 articles relevant to the present review.

Discussion

Exosomes may represent the future of biomarkers in medicine because they may contain disease biomarkers or they may be the vectors for a variety of molecules, including protein and nucleic acids. This theranostic approach has potential in the field of personalized medicine because it allows for targeting the diseased areas in individual patients, possibly at early clinical stages. Increasing evidence indicates that brain inflammation contributes to the pathogenesis of many neuroimmune and

Conclusions

The function of exosomes appears to be much more than just a secretory mechanism of cellular contents. It is a sophisticated means of processing specific molecules, and the versatile role of exosomes opens up new perspectives for the understanding and treatment of neurologic diseases. Further studies are needed to evaluate the potential of exosome-derived miRNAs as biomarkers for diseases. Furthermore, the rapid development of exosome nanotechnology may add alternative-therapeutics delivery to

Conflicts of Interest

The authors have indicated that they have no conflicts of interest with regard to the content of this article.

Acknowledgments

Dr. Conti helped research the literature, Dr. Theoharides researched the literature and wrote the paper, Mrs. Amanda Gross and Smaro Panagiotidou helped design the figure.

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