Altered iron metabolism in postmortem white matter tissue of patients with multiple sclerosis

Document Type : Original Research

Authors
R. doost 1
Y. Fathollahi 1
M. Javan 2
1 Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
2 1 Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.2 Institute for Brain and Cognition, Tarbiat Modares University, Tehran, Iran.
Abstract
Introduction: Iron is an essential element that works as a cofactor in mitochondrial respiration, neurotransmitter biosynthesis, and myelination enzymes. Several pieces of evidence reveal that iron accumulates in demyelinating lesions in patients with multiple sclerosis (MS), and its intracellular homeostasis is disrupted, which exacerbates inflammation and demyelination.

Methods: We reanalyzed a microarray human MS dataset from GEO DataSests, under accession number GSE108000. We examined differentially expressed genes involved in iron metabolism between different types of MS lesions and peri-lesional normal-appearing white matter (PL-NAWM). We used GEO2R for differential expression analysis and created volcano plots, Venn diagrams, and pie charts for data visualization using RStudio software.

Results: We identified 58 genes involved in iron metabolism within the dataset. The expression of key iron-regulating genes, responsible for iron uptake, storage, and export, including CYBRD1, STEAP3, SLC39A14, FTL, FTH1, and CP were significantly changed. We also indicated significant alterations in the iron regulatory pathways in MS lesions and the PL-NAWM. The most prominent alterations were related to the iron uptake pathway, which showed enhanced activity.

Conclusion: Significant changes in iron regulatory gene expressions across MS lesions and the PL-NAWM may lead to dysregulation in iron homeostasis. This imbalance likely contributes to neurodegenerative processes associated with MS. The modifications in the PL-NAWM can be regarded as early-disease indicators. Recognizing these molecular changes provides valuable insights for facilitating timely MS diagnosis and developing targeted therapeutic strategies.

Keywords

Subjects

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Pathobiology Reserach
Volume 27, Issue 1
May 2024
Pages 27-43