Abstract
Extracellular vesicles (EVs) shed by neurons and glia in the central nervous system carry a cargo of specific bioactive molecules, facilitating intercellular communication. However, in neurodegenerative disease conditions, EVs carry pathological miRNAs and/or proteins involved in spreading the disease. Such EVs are also found in the cerebrospinal fluid (CSF) or the circulating blood, the characterization of which could identify biomarkers linked to specific neurodegenerative diseases. Moreover, EVs secreted by various stem/progenitor cells carry therapeutic miRNAs and proteins, which have shown promise to alleviate symptoms and slow down the progression of neurodegenerative diseases. The ability of exogenously administered EVs to easily cross the blood-brain barrier with no risk for thrombosis and incorporate into neurons and glia has also opened up the possibility of using nano-sized EVs as carriers of therapeutic drugs or bioactive proteins. This review summarizes the role and function of EVs in alpha-synuclein-mediated neurodegeneration and the spread of alpha-synuclein from neurons to glia, leading to the activation of the inflammatory response in Parkinson’s disease (PD). Moreover, the promise of brain-derived EVs in the CSF and the circulating blood for biomarker discovery and the efficacy of stem/progenitor cell-derived EVs or EVs loaded with bioactive molecules such as dopamine, catalase, curcumin, and siRNAs, in alleviating Parkinsonian symptoms are discussed.
Highlights
Parkinson's disease (PD), an advancing movement disorder and the most common neurodegenerative disease after Alzheimer’s disease, afflicts ~2% of the world’s population aged >65 years [1]
Shi and colleagues purified central nervous system (CNS)-specific Extracellular vesicles (EVs) in the blood by selectively precipitating L1 cell adhesion molecule (L1CAM) positive EVs and demonstrated that α-syn in such EVs are derived from the CNS [48]. They showed that the concentration of α-syn in CNS-derived EVs in the plasma is substantially higher in PD patients and α-syn levels in such EVs correlated with the disease severity, which supported the value of characterizing αsyn in CNS-derived EVs from the plasma as a biomarker of PD [48]
Conclusions and future perspectives In PD, EV-mediated release of both monomeric and oligomeric forms of α-syn, and increased propensity of EV-associated α-syn to aggregation potentially due to the presence of gangliosides, have been observed
Summary
Parkinson's disease (PD), an advancing movement disorder and the most common neurodegenerative disease after Alzheimer’s disease, afflicts ~2% of the world’s population aged >65 years [1]. EVs secreted by stem/progenitor cells carry therapeutic miRNAs and proteins, which could provide neuroprotection, reduce oxidative stress and neuroinflammation, increase neurogenesis, and improve cognitive and mood function in disease states [19-21, 2832]. From this perspective, currently, there is a considerable interest to use EVs secreted from a variety of stem/progenitor cells and EVs fortified with unique miRNAs, mRNAs, and proteins to stimulate tissue repair and regeneration after injury or disease. The last section discusses the prospects of stem cell-derived EVs for treating PD
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