Trends in Neurosciences
ReviewNeuroimmune Crosstalk through Extracellular Vesicles in Health and Disease
Section snippets
CNS Cells and EVs in Health and Disease
Neurons and glial cells (see Glossary) orchestrate CNS homeostasis through multiple mechanisms of transcellular communication known as ‘neuroimmune interactions’. These interactions range from local cell-to-cell direct contact to the use of soluble factors for short and long-distance transfer of biological material. As described decades ago, EVs appear to be potent mediators of intercellular communication, and have garnered substantial attention as a fundamental component of neuroimmune
Neuroimmune Communication with EVs
The intersection of immunology and neuroscience has been receiving increasing interest in recent years, as more research reveals multiple functional connections between the immune and nervous systems. Understanding this convergence is of particular importance in the CNS, where microglia, the resident immune cells of the brain, closely interact with neurons during development and adulthood for the maintenance of brain homeostasis and innate immune response to CNS insults. Communication between
EV-Mediated Crosstalk in CNS Homeostasis
EV-mediated crosstalk between CNS cells is mediated by EV cargo content as well as direct surface contact, and occurs in an omnidirectional manner, where all cell types influence and communicate with one another. This section describes the functional role of EVs relative to CNS cell types in a homeostatic state.
EV Crosstalk in CNS Disease
Cumulative evidence over the last few decades has shed light on the role of EVs in neurodegenerative disease pathogenesis and progression. Neurodegenerative diseases are characterized by a progressive and irreversible loss of neurons, the aggregation of misfolded proteins in the brain, and widespread neuroinflammation. EVs’ contribution to disease progression has been described in AD, amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), multiple sclerosis (MS), Parkinson’s disease
Concluding Remarks and Future Perspectives
The accumulated findings regarding EV biogenesis, secretion, and uptake have allowed us to better understand their role in modulating CNS function under normal and pathological conditions. EVs represent a unique mode of intercellular communication, which allows proximal and distant interactions among multiple cell types in the CNS and periphery. EVs are involved in a wide variety of homeostatic processes, including modulation of neuronal excitability, synaptic plasticity, myelination,
Acknowledgments
We would like to thank Dr Seiko Ikezu for the scientific guidance and critical editing of this manuscript. This work is funded in part by Nancy Lurie Marks Family Foundation (T.I.), Robert E. Landreth and Dona Landreth Family Foundation (T.I.), BrightFocus Foundation (A2016551S), Cure Alzheimer’s Fund, NIH R01AG054672 (T.I.), RF1AG054199 (T.I.), R56AG057469 (T.I.), and 5T32GM008541 (S.H.).
Glossary
- Alzheimer’s disease (AD)
- a chronic neurodegenerative disease resulting in increased decline in cognitive function over time.
- AMPA
- α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. An ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission within the CNS.
- Amyloid-β peptide (Aβ)
- peptides of 36–43 amino acids, which are found as accumulated plaques in the brains of patients with AD. Amyloid-β proteins are fragments of the cleaved amyloid precursor protein.
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