Dysregulated Iron Homeostasis as Common Disease Etiology and Promising Therapeutic Target
Iron is irreplaceably required for animal and human cells as it provides the activity center for a wide variety of essential enzymes needed for energy production, nucleic acid synthesis, carbon metabolism and cellular defense. However, iron is toxic when present in excess and its uptake and storage...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/12/3/671 |
| _version_ | 1797613782297477120 |
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| author | Bruce E. Holbein Christian Lehmann |
| author_facet | Bruce E. Holbein Christian Lehmann |
| author_sort | Bruce E. Holbein |
| collection | DOAJ |
| description | Iron is irreplaceably required for animal and human cells as it provides the activity center for a wide variety of essential enzymes needed for energy production, nucleic acid synthesis, carbon metabolism and cellular defense. However, iron is toxic when present in excess and its uptake and storage must, therefore, be tightly regulated to avoid damage. A growing body of evidence indicates that iron dysregulation leading to excess quantities of free reactive iron is responsible for a wide range of otherwise discrete diseases. Iron excess can promote proliferative diseases such as infections and cancer by supplying iron to pathogens or cancer cells. Toxicity from reactive iron plays roles in the pathogenesis of various metabolic, neurological and inflammatory diseases. Interestingly, a common underlying aspect of these conditions is availability of excess reactive iron. This underpinning aspect provides a potential new therapeutic avenue. Existing hematologically used iron chelators to take up excess iron have shown serious limitations for use but new purpose-designed chelators in development show promise for suppressing microbial pathogen and cancer cell growth, and also for relieving iron-induced toxicity in neurological and other diseases. Hepcidin and hepcidin agonists are also showing promise for relieving iron dysregulation. Harnessing iron-driven reactive oxygen species (ROS) generation with ferroptosis has shown promise for selective destruction of cancer cells. We review biological iron requirements, iron regulation and the nature of iron dysregulation in various diseases. Current results pertaining to potential new therapies are also reviewed. |
| first_indexed | 2024-03-11T07:00:32Z |
| format | Article |
| id | doaj.art-67e310161b1d49d79ea664490313ca35 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T07:00:32Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-67e310161b1d49d79ea664490313ca352023-11-17T09:18:08ZengMDPI AGAntioxidants2076-39212023-03-0112367110.3390/antiox12030671Dysregulated Iron Homeostasis as Common Disease Etiology and Promising Therapeutic TargetBruce E. Holbein0Christian Lehmann1Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 1X5, CanadaDepartment of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS B3H 1X5, CanadaIron is irreplaceably required for animal and human cells as it provides the activity center for a wide variety of essential enzymes needed for energy production, nucleic acid synthesis, carbon metabolism and cellular defense. However, iron is toxic when present in excess and its uptake and storage must, therefore, be tightly regulated to avoid damage. A growing body of evidence indicates that iron dysregulation leading to excess quantities of free reactive iron is responsible for a wide range of otherwise discrete diseases. Iron excess can promote proliferative diseases such as infections and cancer by supplying iron to pathogens or cancer cells. Toxicity from reactive iron plays roles in the pathogenesis of various metabolic, neurological and inflammatory diseases. Interestingly, a common underlying aspect of these conditions is availability of excess reactive iron. This underpinning aspect provides a potential new therapeutic avenue. Existing hematologically used iron chelators to take up excess iron have shown serious limitations for use but new purpose-designed chelators in development show promise for suppressing microbial pathogen and cancer cell growth, and also for relieving iron-induced toxicity in neurological and other diseases. Hepcidin and hepcidin agonists are also showing promise for relieving iron dysregulation. Harnessing iron-driven reactive oxygen species (ROS) generation with ferroptosis has shown promise for selective destruction of cancer cells. We review biological iron requirements, iron regulation and the nature of iron dysregulation in various diseases. Current results pertaining to potential new therapies are also reviewed.https://www.mdpi.com/2076-3921/12/3/671iron homeostasisiron dysregulationinflammationinfectioncanceriron chelation |
| spellingShingle | Bruce E. Holbein Christian Lehmann Dysregulated Iron Homeostasis as Common Disease Etiology and Promising Therapeutic Target Antioxidants iron homeostasis iron dysregulation inflammation infection cancer iron chelation |
| title | Dysregulated Iron Homeostasis as Common Disease Etiology and Promising Therapeutic Target |
| title_full | Dysregulated Iron Homeostasis as Common Disease Etiology and Promising Therapeutic Target |
| title_fullStr | Dysregulated Iron Homeostasis as Common Disease Etiology and Promising Therapeutic Target |
| title_full_unstemmed | Dysregulated Iron Homeostasis as Common Disease Etiology and Promising Therapeutic Target |
| title_short | Dysregulated Iron Homeostasis as Common Disease Etiology and Promising Therapeutic Target |
| title_sort | dysregulated iron homeostasis as common disease etiology and promising therapeutic target |
| topic | iron homeostasis iron dysregulation inflammation infection cancer iron chelation |
| url | https://www.mdpi.com/2076-3921/12/3/671 |
| work_keys_str_mv | AT bruceeholbein dysregulatedironhomeostasisascommondiseaseetiologyandpromisingtherapeutictarget AT christianlehmann dysregulatedironhomeostasisascommondiseaseetiologyandpromisingtherapeutictarget |