2. Academic Validation
  3. Deferoxamine-induced neurotoxicity: Role of chaperone-mediated autophagy dysfunction in neuronal apoptosis in the hippocampus

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

  • Chem Biol Interact. 2025 Jan 25:406:111341. doi: 10.1016/j.cbi.2024.111341.
Hong Zhang 1,  Jian Guo 2,  Jiayi Chu 3,  Huanhuan Yu 4,  Jialin Zhang 1,  Siman Ma 3,  Ge Jin 5,  Yingshan Jiang 3,  Jiao Xiao 6,  Yutong Hou 3,  Minyan Li 7,  Shiliang Yin 8
Affiliations

Affiliations

  • 1 School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
  • 2 School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China; Shenyang Kangende Medical Technology Co., Ltd, Shenyang, 110163, People's Republic of China.
  • 3 School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
  • 4 Department of Hematology, General Hospital of Northern Theater Command, Shenyang, 110016, People's Republic of China.
  • 5 School of Pharmacy, Shenyang Medical College, Shenyang, 110034, People's Republic of China.
  • 6 Wuya School of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
  • 7 Department of Hematology, General Hospital of Northern Theater Command, Shenyang, 110016, People's Republic of China. Electronic address: limy2013@sina.com.
  • 8 School of Pharmacy, Shenyang Medical College, Shenyang, 110034, People's Republic of China. Electronic address: yslal@163.com.
PMID: 39643152 DOI: 10.1016/j.cbi.2024.111341
Abstract

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.

Keywords

Chaperon mediated autophagy; Deferoxamine mesylate; Neuronal adverse events; Neuronal apoptosis.

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