Role of Glia-Derived Extracellular Vesicles in Neurodegenerative Diseases

Abstract

Extracellular vesicles (EVs), as nano-sized vesicles secreted by almost all cells, have been recognized as the essential transmitter for cell-to-cell communication and participating in multiple biological processes. Neurodegenerative diseases (ND), such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, share common mechanisms of the aggregation and propagation of distinct pathologic proteins among cells in the nervous systems and neuroinflammatory reactions mediated by glia during the pathogenic process. This feature indicates the vital role of crosstalk between neurons and glia in the pathogenesis of ND. In recent years, glia-derived EVs have been investigated as potential mediators of signals between neurons and glia, which provides a new direction and strategy for understanding ND. By a comprehensive summary, it can be concluded that glia-derived EVs have both a beneficial and/or a detrimental effect in the process of ND. Therefore, this review article conveys the role of glia-derived EVs in the pathogenesis of ND and raises current limitations of their potential application in the diagnosis and treatment of ND.

Small Extracellular Vesicles of M1-BV2 Microglia Induce Neuronal PC12 Cells Apoptosis via the Competing Endogenous Mechanism of CircRNAs

“…Microglia can communicate with neurons through secretion of SEVs. The secreted SEVs of microglia can participate in the metabolism of neurons, regulating the synaptic activity and neuronal survival [ 38 ]. Recent studies have shown that SEVs released by pro-inflammatory microglia (M1 phenotype) have been shown to contribute to the progressive neuroinflammatory response and thus drive neurodegeneration [ 39 ].…”

“…Recent studies have shown that SEVs released by pro-inflammatory microglia (M1 phenotype) have been shown to contribute to the progressive neuroinflammatory response and thus drive neurodegeneration [ 39 ]. SEVs from M1 microglia can also block remyelination in neurodegenerative diseases [ 38 ]. We found that SEVs released by activated M1-BV2 microglia can shorten and decrease the number of neurites, which may further induce neurological dysfunction.…”

The Physio-Pathological Role of Group I Metabotropic Glutamate Receptors Expressed by Microglia in Health and Disease with a Focus on Amyotrophic Lateral Sclerosis

“…Released extracellular vesicles mediate neurotoxicity mainly by transferring pro-inflammatory cytokines [ 130 , 136 ] or even modulating protein aggregation, as in the case of β-amyloid [ 137 ]. Furthermore, extracellular vesicles were increased in the human and rodent cerebrospinal fluid during cerebral inflammation, supporting their role in the spread of the inflammatory process [ 135 , 138 ] and in neurodegenerative diseases [ 139 , 140 , 141 , 142 ].…”

Exosomes in Alpha-Synucleinopathies: Propagators of Pathology or Potential Candidates for Nanotherapeutics?

“…The communication between neuronal and glial cells is a crucial determinant for the maintenance of cellular homeostasis in the brain [ 46 ], with glia reported to exert both neurotoxic and neuroprotective functions in neurons via the release of extracellular vesicles [ 47 ] ( Figure 1 ). A pioneering study by Potolicchio and colleagues in 2005, suggested that exosomes derived from N9 microglial cells contained the aminopeptidase CD13, which is responsible for the degradation of neuropeptides, thus playing a role in neuronal metabolic support and neuropeptide catabolism [ 20 ].…”