Fading Blue: Exploring the Causes of Locus Coeruleus Damage Across the Lifespan

Locus Coeruleus (LC) is a brain nucleus that is involved in a variety of key functions (ranging from attention modulation to sleep–wake cycle regulation, to memory encoding); its proper function is necessary both during brain development and for brain integrity maintenance, and both at the microscale and macroscale level. Due to their specific intrinsic and extrinsic features, LC cells are considered particularly susceptible to damage concerning a variety of insults. This explains LC involvement in degenerative diseases not only in adults (in the context of neurodegenerative disease, mainly), but also in children (in relation to early hypoxic damage and Down’s Syndrome, among others). In this narrative review, we dissect the potential mechanisms through which LC is affected in different diseases, with a special emphasis on the high rate of activity it is subjected to and the oxidative stress associated with it. Further research aimed at deepening our understanding of these mechanisms is needed to enable the development of potential strategies in the future that could slow down LC degeneration in subjects predisposed to specific brain disorders.