Mechanisms of axonal support by oligodendrocyte-derived extracellular vesicles

Extracellular vesicles (EVs) have recently emerged as versatile elements of cell communication in the nervous system, mediating tissue homeostasis. EVs influence the physiology of their target cells via horizontal transfer of molecular cargo between cells and by triggering signalling pathways. In this Review, we discuss recent work revealing that EVs mediate interactions between oligodendrocytes and neurons, which are relevant for maintaining the structural integrity of axons. In response to neuronal activity, myelinating oligodendrocytes release EVs, which are internalized by neurons and provide axons with key factors that improve axonal transport, stress resistance and energy homeostasis. Glia-to-neuron transfer of EVs is thus a crucial facet of axonal preservation. When glial support is impaired, axonal integrity is progressively lost, as observed in myelin-related disorders, other neurodegenerative diseases and with normal ageing. We highlight the mechanisms that oligodendroglial EVs use to sustain axonal integrity and function. Oligodendrocytes secrete extracellular vesicles, which deliver cargo to axons where they regulate key cellular processes. In this Review, Kramer-Albers and Werner discuss the mechanisms by which extracellular vesicles promote neuronal health and their potential to be utilized therapeutically.

Automated summary

Extracellular vesicles (EVs) have been identified as important mediators of cell communication in the nervous system, particularly between oligodendrocytes and neurons. EVs play a crucial role in maintaining the structural integrity of axons by delivering key factors that improve axonal transport, stress resistance, and energy homeostasis. Dysfunction in glial support and the transfer of EVs can lead to loss of axonal integrity observed in myelin-related disorders, neurodegenerative diseases, and ageing. Understanding the mechanisms of EV-mediated interactions is essential for therapeutic applications.