Deferoxamine-induced neurotoxicity: Role of chaperone-mediated autophagy dysfunction in neuronal apoptosis in the hippocampus

Deferoxamine mesylate (DFX) is a microorganism-derived iron chelator used in hematology to treat acute iron intoxication and chronic iron overload. Many studies have reported adverse neurological events from DFX exposure, but it is challenging to distinguish these from the effects of iron intoxication. This study aimed to evaluate whether DFX exposure alone can directly impair neurological functions and to elucidate its toxicological mechanisms. Our findings from in vivo and in vitro experiments indicate that DFX exposure can directly cause emotional and cognitive dysfunction in mice. Neuronal apoptosis, resulting from chaperone-mediated autophagy (CMS) dysfunction, was identified as a key toxicological mechanism underlying DFX-induced neuronal impairment. This study provides evidence for the comprehensive monitoring and timely management of neurotoxic adverse events associated with DFX exposure, as well as a foundation for developing medications to prevent and treat these events to enhance patient quality of life.