Microglia-derived extracellular vesicles in homeostasis and demyelination/remyelination processes

WIES MANCINI VSB, MATTERA VS, PASQUINI JM, CORREALE J AND PASQUII LAUINI JM, CORREALE JI JM

JOURNAL OF NEUROCHEMISTRY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2024 vol. 168 p. 3 - 25

0022-3042

Microglia (MG) play a crucial role as the predominant myeloid cells in the central nervoussystem and are commonly activated in multiple sclerosis. They perform essentialfunctions under normal conditions, such as actively surveying the surrounding parenchyma,facilitating synaptic remodeling, engulfing dead cells and debris, and protectingthe brain against infectious pathogens and harmful self-proteins. Extracellularvesicles (EVs) are diverse structures enclosed by a lipid bilayer that originate fromintracellular endocytic trafficking or the plasma membrane. They are released by cellsinto the extracellular space and can be found in various bodily fluids. EVs have recentlyemerged as a communication mechanism between cells, enabling the transferof functional proteins, lipids, different RNA species, and even fragments of DNA fromdonor cells. MG act as both source and recipient of EVs. Consequently, MG-derivedEVs are involved in regulating synapse development and maintaining homeostasis.These EVs also directly influence astrocytes, significantly increasing the release of inflammatorycytokines like IL-1β, IL-6, and TNF-α, resulting in a robust inflammatory response.Furthermore, EVs derived from inflammatory MG have been found to inhibitremyelination, whereas Evs produced by pro-regenerative MG effectively promotemyelin repair. This review aims to provide an overview of the current understanding ofMG-derived Evs, their impact on neighboring cells, and the cellular microenvironmentin normal conditions and pathological states, specifically focusing on demyelinationand remyelination processes.