Recent advances in extracellular vesicles in ALS and emergent perspectives

Amyotrophic lateral sclerosis (ALS) is a severe and incurable neurodegenerative disease characterized by the progressive death of motor neurons, leading to paralysis and death. It is a rare disease characterized by high patient-to-patient heterogeneity, which makes its study arduous and complex. Extracellular vesicles (EVs) have emerged as important players in the development of ALS. Thus, ALS phenotype-expressing cells can spread their abnormal bioactive cargo through the secretion of EVs, even in distant tissues. Importantly, owing to their nature and composition, EVs’ formation and cargo can be exploited for better comprehension of this elusive disease and identification of novel biomarkers, as well as for potential therapeutic applications, such as those based on stem cell-derived exosomes. Researchers at the University of Coimbra highlight recent advances in the identification of the role of EVs in ALS etiopathology and how EVs can be promising new therapeutic strategies.

The role of EVs in ALS

EVs contribute to the pathogenesis of ALS (left reddish side). EVs are produced by different cell types in the central nervous system and neuromuscular junctions. In the context of ALS, EVs may carry disease-related biological molecules (proteins and miRNAs) involved in the transformation and degeneration of the brain and neuromuscular elements, thus contributing to the spread of the pathology between different cell types. Furthermore, EVs can reach long distances in the body, contributing to the exchange of harmful molecules between the brain and neuromuscular junction. Considering this, the molecules transported by EVs circulating in the bloodstream and cerebrospinal fluid are considered potential biomarkers for the diagnosis and prognosis of ALS. Finally, EVs have a therapeutic potential. Blocking the exchange of EVs carrying harmful molecules and administering EVs with neuroprotective cargo may slow the progression of ALS or revert its pathological effects (right-greenish side). ALS, amyotrophic lateral sclerosis, EV, extracellular vesicle; miRNA, microRNA.