Abstract
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.
Highlights
Parkinson’s disease (PD) is the second most common chronic neurodegenerative disorder (ND) after Alzheimer’s [1]
Astrocytes from the ventral midbrain are pivotal for the development of DAergic neurons, thanks to the release of an array of pro-survival and neuroprotective molecules [71,72,73,74,75], such as the glial-derived neurotrophic factor (GDNF) [76] and the basic fibroblast growth factor [77], whose levels are altered in PD patients [78,79]
Extracellular vesicles (EVs)-DJ-1 levels are higher in PD subjects compared to controls, even if further studies need to confirm its validity as a novel PD biomarker [164,175,176]
Summary
Parkinson’s disease (PD) is the second most common chronic neurodegenerative disorder (ND) after Alzheimer’s [1]. The different range and onset of the non-motor symptoms during PD progression reflect distinct PD phenotypes [14] In this regard, in 2015 “The International Parkinson and Movement Disorder Society” defined several criteria to identify and stratify PD, which were validated by many clinical studies [17,18,19]. In 1983, Harding and colleagues demonstrated the existence inside rat reticulocytes of multivesicular endosomes that fused back with the plasma membrane to release their vesicular content [33] These particular vesicles were obtained in the same year by Pan and Johnson after 1h of 100,000× g ultracentrifugation, starting from sheep reticulocytes-derived supernatants [34]. Exosomes are produced by the inward budding of the endosomal compartment, forming the so-called “multivesicular body” (MVB) These intraluminal vesicles are subsequently released outside the cell after the fusion of the MVB with the plasma membrane. Biomolecules 2020, 10, 1327 potential of both natural and engineered EVs, and the possibility to use them as advanced drug delivery systems in PD
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