Peptidylarginine deiminases are a family of
calcium-activated
enzymes with multifaceted roles in physiological and
pathological processes, including in the central nervous system.
Peptidylarginine deiminases cause post-translational deimination/citrullination, leading to changes in structure and function of a wide range of target
proteins. Deimination can facilitate
protein moonlighting, modify
protein-
protein interaction, cause
protein dysfunction and induce inflammatory responses.
Peptidylarginine deiminases also regulate the biogenesis of extracellular vesicles, which play important roles in cellular communication through transfer of extracellular vesicle-cargo, e.
g., proteins and genetic material. Both
peptidylarginine deiminases and extracellular vesicles are linked to a number of pathologies, including in the central nervous system, and their modulation with pharmacological
peptidylarginine deiminase inhibitors have shown great promise in several in vitro and in vivo
central nervous system disease models. Furthermore, extracellular vesicles derived from mesenchymal stem cells have been assessed for their therapeutic application in central nervous system injury. As circulating extracellular vesicles can be used as non-invasive liquid biopsies, their specific cargo-signatures (including deiminated
proteins and
microRNAs) may allow for disease "fingerprinting" and aid early
central nervous system disease diagnosis, inform
disease progression and response to
therapy. This mini-review discusses recent advances in the field of
peptidylarginine deiminase and extracellular vesicle research in the central nervous system, focusing on several central nervous system acute injury, degeneration and
cancer models.