Extracellular Vesicles in the Development of Neurodegenerative Conditions

A broad discussion of extracellular vesicles is really a broad discussion of cell communication, as much of the traffic of molecules between cells is carried inside vesicles. Researchers here discuss what is known of the roles played by vesicle-mediated communication in neurodegenerative conditions, still a very broad topic. One of the noteworthy contributions is that this traffic of vesicles enables the spread of prion-like altered and misfolded proteins, such as tau and α-synuclein, that are capable of seeding the generation of more such harmful molecules in the destination cell. Whether there are ways to selectively prevent this process of spread and seeding remains an open question; it seems a daunting prospect, since every part of the vesicle communication infrastructure performs useful functions.

Many neurodegenerative disorders are characterized by the abnormal aggregation of misfolded proteins that form amyloid deposits which possess prion-like behavior such as self-replication, intercellular transmission, and consequent induction of native forms of the same protein in surrounding cells. The distribution of the accumulated proteins and their correlated toxicity seem to be involved in the progression of nervous system degeneration. Molecular chaperones are known to maintain proteostasis, contribute to protein refolding to protect their function, and eliminate fatally misfolded proteins, prohibiting harmful effects. However, chaperone network efficiency declines during aging, prompting the onset and the development of neurological disorders.

Extracellular vesicles (EVs) are tiny membranous structures produced by a wide range of cells under physiological and pathological conditions, suggesting their significant role in fundamental processes particularly in cellular communication. They modulate the behavior of nearby and distant cells through their biological cargo. In the pathological context, EVs transport disease-causing entities, including prions, α-synuclein, and tau, helping to spread damage to non-affected areas and accelerating the progression of neurodegeneration. However, EVs are considered effective for delivering therapeutic factors to the nervous system, since they are capable of crossing the blood-brain barrier (BBB) and are involved in the transportation of a variety of cellular entities.

Here, we review the neurodegeneration process caused mainly by the inefficiency of chaperone systems as well as EV performance in neuropathies, their potential as diagnostic biomarkers and a promising EV-based therapeutic approach.

Link: https://doi.org/10.3390/ijms24020927

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