The complexity of extracellular vesicles: Bridging the gap between cellular communication and neuropathology

Apr 23, 2024Journal of neurochemistry

Extracellular Vesicles: Linking Cell Communication to Brain Disease

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Abstract

Brain-derived extracellular vesicles (EVs) are linked to both neurodegeneration and potential therapeutic strategies.

EVs play a role in clearing and transporting proteins and nucleic acids, responding to cellular changes associated with neurodegeneration.
In conditions like Alzheimer's and Parkinson's diseases, EVs are involved in spreading harmful proteins that may worsen neurodegeneration.
The mechanisms that determine whether EVs have protective or harmful effects in neurodegenerative diseases are not yet fully understood.
EVs have the ability to cross the blood-brain barrier, presenting opportunities for new diagnostic and treatment approaches.

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Brain-derived extracellular vesicles (EVs) serve a prominent role in maintaining homeostasis and contributing to pathology in health and disease. This review establishes a crucial link between physiological processes leading to EV biogenesis and their impacts on disease. EVs are involved in the clearance and transport of proteins and nucleic acids, responding to changes in cellular processes associated with neurodegeneration, including autophagic disruption, organellar dysfunction, aging, and other cell stresses. In neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, etc.), EVs contribute to the spread of pathological proteins like amyloid β, tau, ɑ-synuclein, prions, and TDP-43, exacerbating neurodegeneration and accelerating disease progression. Despite evidence for both neuropathological and neuroprotective effects of EVs, the mechanistic switch between their physiological and pathological functions remains elusive, warranting further research into their involvement in neurodegenerative disease. Moreover, owing to their innate ability to traverse the blood-brain barrier and their ubiquitous nature, EVs emerge as promising candidates for novel diagnostic and therapeutic strategies. The review uniquely positions itself at the intersection of EV cell biology, neurophysiology, and neuropathology, offering insights into the diverse biological roles of EVs in health and disease.

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