Hemochromatosis associated with Parkinson's Disease
DOI:
https://doi.org/10.33448/rsd-v14i8.49294Keywords:
Hemochromatosis, Parkinson's disease, Physiology.Abstract
Iron is an essential mineral found in all living organisms and plays a key role in numerous physiological processes, including growth, development, and various cellular functions. This study aims to review the literature on the association between iron metabolism, hemochromatosis, and Parkinson’s disease (PD), assessing how iron accumulation may negatively affect health and potentially contribute to the development or progression of PD. This is a qualitative literature review conducted in August 2024. The research was carried out using the Scopus and PubMed databases, resulting in the selection of 25 studies. The objective was to analyze the role of iron accumulation in PD, identifying patterns and gaps in current evidence. In the nervous system, iron plays a critical role in mitochondrial respiration, myelin formation, and neurotransmitter metabolism—functions essential for maintaining neuronal health and cognitive performance. However, excess iron can lead to the production of free radicals, causing oxidative damage that significantly contributes to the onset of various pathological conditions. Since the human body lacks widely efficient mechanisms to eliminate excess iron, the regulation of its absorption, transport, and storage is crucial to prevent toxicity and its harmful effects on the nervous system.
References
Afzal, S., Abdul Manap, A. S., Attiq, A., Albokhadaim, I., Kandeel, M., & Alhojaily, S. M. (2023). From imbalance to impairment: the central role of reactive oxygen species in oxidative stress-induced disorders and therapeutic exploration. Frontiers in pharmacology, 14, 1269581. https://doi.org/10.3389/fphar.2023.1269581
Asano, T., Koike, M., Sakata, S., Takeda, Y., Nakagawa, T., Hatano, T., et al. (2015). Possible involvement of iron-induced oxidative insults in neurodegeneration. Neuroscience Letters, 588, 29–35. https://dx.doi.org/10.1016/j.neulet.2014.12.052
Belaidi, A. A., & Bush, A. I. (2016). Iron neurochemistry in Alzheimer’s disease and Parkinson’s disease: Targets for therapeutics. Journal of Neurochemistry, 139(Suppl 1), 179–197. https://doi.org/ 10.1111/jnc.13425
Bouchaoui, H., Mahoney-Sanchez, L., Garçon, G., Berdeaux, O., Alleman, L. Y., Devos, D., et al. (2023). ACSL4 and the lipoxygenases 15/15B are pivotal for ferroptosis induced by iron and PUFA dyshomeostasis in dopaminergic neurons. Free Radical Biology and Medicine, 195, 145–157. https://10.1016/j.freeradbiomed.2022.12.086
Carmona, A., Carboni, E., Gomes, L. C., Roudeau, S., Maass, F., Lenz, C., et al. (2024). Metal dyshomeostasis in the substantia nigra of patients with Parkinson’s disease or multiple sclerosis. Journal of Neurochemistry, 168(2), 128–141. https://doi.org/10.1111/jnc.16040
Casanova, F., Tian, Q., Williamson, D. S., Qian, Y., Zweibaum, D., Ding, J., et al. (2024). MRI-derived brain iron, grey matter volume, and risk of dementia and Parkinson’s disease: Observational and genetic analysis in the UK Biobank cohort. Neurobiology of Disease, 197, 1–7. https://doi.org/10.1016/j.nbd.2024.106539
Cheng, R., Dhorajia, V. V., Kim, J., & Kim, Y. (2022). Mitochondrial iron metabolism and neurodegenerative diseases. Neurotoxicology, 88, 88–101. https://doi.org/10.1016/j.neuro.2021.11.003
Ci, Y. Z., Li, H., You, L. H., Jin, Y., Zhou, R., Gao, G., et al. (2020). Iron overload induced by IRP2 gene knockout aggravates symptoms of Parkinson's disease. Neurochemistry international, 134, 104657. https://doi.org/10.1016/j.neuint.2019.104657
Henrich, M. T., Oertel, W. H., Surmeier, D. J., & Geibl, F. F. (2023). Mitochondrial dysfunction in Parkinson's disease - a key disease hallmark with therapeutic potential. Molecular neurodegeneration, 18(1), 83. https://doi.org/10.1186/s13024-023-00676-7
Hinarejos, I., Machuca-Arellano, C., Sancho, P., & Espinós, C. (2020). Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA). Antioxidants (Basel, Switzerland), 9(10), 1020. https://doi.org/10.3390/antiox9101020
Jiménez-Jiménez, F. J., Alonso-Navarro, H., García-Martín, E., & Agúndez, J. A. G. (2021). Biological fluid levels of iron and iron-related proteins in Parkinson's disease: Review and meta-analysis. European journal of neurology, 28(3), 1041–1055. https://doi.org/10.1111/ene.14607
Kulaszyńska, M., Kwiatkowski, S., & Skonieczna-Żydecka, K. (2024). The Iron Metabolism with a Specific Focus on the Functioning of the Nervous System. Biomedicines, 12(3), 595. https://doi.org/10.3390/biomedicines12030595
Lancione, M., Donatelli, G., Del Prete, E., Campese, N., Frosini, D., Cencini, M., et al. (2022). Evaluation of iron overload in nigrosome 1 via quantitative susceptibility mapping as a progression biomarker in prodromal stages of synucleinopathies. NeuroImage, 260, 119454. https://doi.org/10.1016/j.neuroimage.2022.119454
Li, B., Xia, M., Zorec, R., Parpura, V., & Verkhratsky, A. (2021). Astrocytes in heavy metal neurotoxicity and neurodegeneration. Brain research, 1752, 147234. https://doi.org/10.1016/j.brainres.2020.147234
Liu, C., Liang, M. C., & Soong, T. W. (2019). Nitric Oxide, Iron and Neurodegeneration. Frontiers in neuroscience, 13, 114. https://doi.org/10.3389/fnins.2019.00114
Maniscalchi, A., Benzi Juncos, O. N., Conde, M. A., Funk, M. I., Fermento, M. E., Facchinetti, M. M., et al. (2024). New insights on neurodegeneration triggered by iron accumulation: Intersections with neutral lipid metabolism, ferroptosis, and motor impairment. Redox Biology, 71, 1–15. https://doi.org/10.1016/j.redox.2024.103074
Negida, A., Hassan, N. M., Aboeldahab, H., Zain, Y. E., Negida, Y., Cadri, S., et al. (2024). Efficacy of the iron-chelating agent, deferiprone, in patients with Parkinson's disease: A systematic review and meta-analysis. CNS neuroscience & therapeutics, 30(2), e14607. https://doi.org/10.1111/cns.14607
Ruan, Z., Zhang, D., Huang, R., Sun, W., Hou, L., Zhao, J., et al. (2022). Microglial Activation Damages Dopaminergic Neurons through MMP-2/-9-Mediated Increase of Blood-Brain Barrier Permeability in a Parkinson's Disease Mouse Model. International journal of molecular sciences, 23(5), 2793. https://doi.org/10.3390/ijms23052793
Sánchez Campos, S., Rodríguez Diez, G., Oresti, G. M., & Salvador, G. A. (2015). Dopaminergic neurons respond to iron-induced oxidative stress by modulating lipid acylation and deacylation cycles. PLoS ONE, 10(6), e0123456. https://doi.org/10.1371/journal.pone.0130726
Virel, A., Faergemann, E., Orädd, G., & Strömberg, I. (2014). Magnetic resonance imaging (MRI) to study striatal iron accumulation in a rat model of Parkinson’s disease. PLoS ONE, 9(11), e0123457. https://doi.org/10.1371/journal.pone.0112941
Vogt, A. S., Arsiwala, T., Mohsen, M., Vogel, M., Manolova, V., & Bachmann, M. F. (2021). On Iron Metabolism and Its Regulation. International journal of molecular sciences, 22(9), 4591. https://doi.org/10.3390/ijms22094591
Wang, R., Wang, Y., Qu, L., Chen, B., Jiang, H., Song, N., et al. (2019). Iron-induced oxidative stress contributes to α-synuclein phosphorylation and up-regulation via polo-like kinase 2 and casein kinase 2. Neurochemistry international, 125, 127–135. https://doi.org/10.1016/j.neuint.2019.02.016
Ward, R. J., Dexter, D. T., & Crichton, R. R. (2022). Iron, Neuroinflammation and Neurodegeneration. International journal of molecular sciences, 23(13), 7267. https://doi.org/10.3390/ijms23137267
Xiao, Z., Wang, X., Pan, X., Xie, J., & Xu, H. (2024). Mitochondrial iron dyshomeostasis and its potential as a therapeutic target for Parkinson's disease. Experimental neurology, 372, 114614. https://doi.org/10.1016/j.expneurol.2023.114614
Zhang, N., Yu, X., Song, L., Xiao, Z., Xie, J., & Xu, H. (2022). Ferritin confers protection against iron-mediated neurotoxicity and ferroptosis through iron chelating mechanisms in MPP+-induced MES23.5 dopaminergic cells. Free radical biology & medicine, 193(Pt2), 751–763. https://doi.org/10.1016/j.freeradbiomed.2022.11.018
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Copyright (c) 2025 David Cohen, Lucas Locatelli Menegaz, Lucas Tiburski Sommer, Hadassa Lucena Sales Santos, Fernanda Cavinatto Pinto, Luiz Carlos Porcello Marrone
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