Relevance Of Exosomes Research Articles

A SHORT EDITORIAL VIEW ON THE RELEVANCE OF EXOSOMES IN SOME NEUROPSYCHIATRIC MANIFESTATIONS - MODEL STUDIES

Exosomes are a class of extracellular vesicles derived from cells of endosomal origin and typically have a diameter between 40 to 100 nm, being the smallest type of extracellular vesicle. Although in recent years, the use of exosomes in experimental studies has increased, currently there are few studies that have as a research subject the neurobehavioral changes that exosomes have on model organisms. For this reason, our group is further looking to develop and apply the methodology regarding the neurobehavioral changes that exosomes have on zebrafish (Danio rerio). Thus, we present here a short editorial view on the relevance of exosomes in some neuropsychiatric manifestations-models studies, as wel as some of our future plans in this new area of reearch.

Role of exosomes in the pathogenesis of inflammation in Parkinson's disease.

Inflammatory responses, including glial cell activation and peripheral immune cell infiltration, are involved in the pathogenesis of Parkinson’s disease (PD). These inflammatory responses appear to be closely related to the release of extracellular vesicles, such as exosomes. However, the relationships among different forms of glial cell activation, synuclein dysregulation, mitochondrial dysfunction, and exosomes are complicated. This review discusses the multiple roles played by exosomes in PD-associated inflammation and concludes that exosomes can transport toxic α-synuclein oligomers to immature neurons and into the extracellular environment, inducing the oligomerization of α-synuclein in normal neurons. Misfolded α-synuclein causes microglia and astrocytes to activate and secrete exosomes. Glial cell-derived exosomes participate in communications between glial cells and neurons, triggering anti-stress and anti-inflammatory responses, in addition to axon growth. The production and release of mitochondrial vesicles and exosomes establish a new mechanism for linking mitochondrial dysfunction to systemic inflammation associated with PD. Given the relevance of exosomes as mediators of neuron-glia communication in neuroinflammation and neuropathogenesis, new targeted treatment strategies are currently being developed that use these types of extracellular vesicles as drug carriers. Exosome-mediated inflammation may be a promising target for intervention in PD patients.

Exosomes as mediators of neuroinflammation

Exosomes are membrane-bound nanovesicles that are shed by cells of various lineages under normal as well as pathological conditions. Previously thought to be ‘extracellular debris’, exosomes have recently generated immense interest following their discovery as mediators of intercellular communication by delivering functional proteins, mRNA transcripts as well as miRNAs to recipient cells. Although suggested to primarily serve as signaling organelles which also remove unwanted cellular components in the brain, accumulating evidence suggests that exosomes can also significantly contribute to the development of several neuropathologies. Toxic forms of aggregated proteins such as α-synuclein, amyloid β and prions, that are responsible for the development of Parkinson’s disease, Alzheimer’s disease and Creutzfeldt-Jacob disease (CJD) respectively, have been shown to get effectively packaged into exosomes and spread from one cell to another, initiating an inflammatory cascade. In addition, exosomes secreted by resident brain cells in response to pathogenic stimuli such as viral proteins can also influence bystander cells by the transfer of dysregulated miRNAs that suppress the expression of essential genes in the recipient cells. Given the relevance of exosomes in brain communication and neuropathogenesis, novel therapeutic strategies are now being developed that exploit the biology of these vesicles to deliver anti-inflammatory molecules to the CNS. Exosomes may alter the way we think about brain disorders and their treatments.