Contribution of Extracellular Vesicles and Molecular Chaperones in Age-Related Neurodegenerative Disorders of the CNS

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, alpha-syn, 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.

Automated summary

Many neurodegenerative disorders are caused by the abnormal aggregation of misfolded proteins, which can self-replicate, transmit between cells, and induce the same protein in nearby cells. The distribution and toxicity of these accumulated proteins are involved in the progression of nervous system degeneration. Molecular chaperones help maintain protein stability and eliminate misfolded proteins, but their efficiency declines with age, leading to the development of neurological disorders. Extracellular vesicles (EVs) play a significant role in cellular communication and can transport disease-causing entities, contributing to the spread of damage in neurodegeneration. However, EVs also show potential in delivering therapeutic factors to the nervous system and can cross the blood-brain barrier (BBB). This review discusses the inefficiency of chaperone systems and the role of EVs in neurodegeneration, their potential as diagnostic biomarkers, and a promising EV-based therapeutic approach.