Inappropriately chelated iron in the cerebrospinal fluid of amyotrophic lateral sclerosis patients

Abstract

ALS is characterized by oxidative damage in the brain and cerebrospinal fluid, which is exerted by pro-oxidative activity of iron. Such activity of iron can be drastically increased in the presence of inappropriate iron ligands that catalyze redox cycling of iron, thereby promoting hydroxyl radical generation. The aim of our study was to determine the relative level of inappropriate iron ligands in the cerebrospinal fluid of ALS patients. To determine the levels of inappropriate iron ligands and redox activity of iron in cerebrospinal fluid (10 samples from ALS patients and 10 controls), we applied electron paramagnetic resonance spectroscopy. We have shown that cerebrospinal fluid of ALS patients comprises two-fold increased level of inappropriate iron ligands, proportionally increasing iron redox activity and hydroxyl radical production compared to controls. In conclusion, our results strongly support the pro-oxidative/detrimental role of inappropriately chelated iron in ALS pathophysiology. The identification of biomolecules that form such iron complexes and their therapeutic targeting may represent the future of ALS treatment.

Key words::

• Amyotrophic lateral sclerosis
• cerebrospinal fluid
• iron
• oxidative stress
• ligands

Acknowledgements

This work has been supported by the Ministry of Education and Science of the Republic of Serbia, grant numbers 175083 and 173014.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.