Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Dec. 5, 2024

Copper (Cu) is essential for brain development and function, yet its overload induces neuronal damage contributes to neurodegeneration other neurological disorders. Multiple studies demonstrated that Cu neurotoxicity associated with mitochondrial dysfunction, routinely assessed by reduction of membrane potential. Nonetheless, the role alterations dynamics in dysfunction induced exposure still debatable. Therefore, objective present narrative review was discuss Cu-induced special emphasis on influence fusion fission, as well clearance mitophagy. Existing data demonstrate that, addition electron transport chain inhibition, damage, reactive oxygen species (ROS) overproduction, overexposure inhibits down-regulation Opa1, Mfn1, Mfn2 expression, while promoting fission through up-regulation Drp1. It has been also PINK1/Parkin-dependent mitophagy cells, considered a compensatory response dysfunction. However, long-term high-dose impairs mitophagy, resulting accumulation dysfunctional mitochondria. inhibition biogenesis due PGC-1α further aggravates brain. Studies from non-brain cells corroborate these findings, offering additional evidence dysregulation may be involved Finally, cuproptosis proteotoxic stress, contribute pathogenesis certain diseases. Based it assumed mitoprotective agents, specifically targeting mechanisms quality control, would useful prevention neurotoxic effects overload.

Language: Английский