Brain rewired: Redox control of brain cell crosstalk via nanotubes and vesicles

Redox balance is critically important for maintaining normal physiological functions in the brain. Disruptions in this balance, whether through excessive reduction (reductive stress) or excessive oxidation (oxidative stress), can contribute to the onset and progression of neuropathological conditions. For decades, research has predominantly focused on the impact of redox imbalance in inducing nervous system damage at the level of single cells, subcellular organelles, and macromolecular changes. Recent evidence increasingly indicates that redox status not only affects intracellular processes but also plays a pivotal role in regulating intercellular communication. Specifically, redox imbalance has been shown to influence the formation of tunnelling nanotubes and the secretion of extracellular vesicles (EVs, such as microvesicles, exosomes), both of which are critical for the transfer of cellular signals, organelles, and biomolecules between cells. In this review, after a succinct introduction to key concepts related to redox biology, we present a comprehensive overview of intercellular communication and its interaction with redox balance in the brain, encompassing both genetic and epigenetic modifications.