Ferroptosis and Iron Homeostasis: Molecular Mechanisms and Neurodegenerative Disease Implications
Abstract
:1. Introduction
2. Significance and Scope
3. Ferroptosis: Core Mechanisms and Iron Regulation
3.1. The System Xc−-GSH-GPX4 Regulatory Axis
3.2. Lipid Peroxidation Drives Ferroptosis
3.3. Reactive Oxygen Species (ROS)
3.4. Mitochondrial Contribution to Ferroptosis
4. Iron Homeostasis and Ferroptosis Regulation
4.1. Regulation of Iron Uptake
4.2. Regulation of Iron Storage and Mobilization
4.3. Iron Regulatory Network
4.4. Regulation of Iron Export
5. Brain-Specific Iron Homeostasis: The Critical Role of the Blood-Brain Barrier
5.1. Iron Functions in the Central Nervous System
5.2. Structure and Function of the Blood-Brain Barrier in Iron Transport
5.3. Iron Distribution and Regulation in the Brain Parenchyma
6. Disruption of Iron Homeostasis in Neurodegenerative Diseases
6.1. Common Pathways of Iron Dysregulation in Neurodegeneration
6.2. Blood-Brain Barrier Dysfunction in Alzheimer’s and Parkinson’s Disease
6.3. Iron Homeostasis and Ferroptosis Susceptibility in Alzheimer’s and Parkinson’s Disease
7. Linking Iron Dysregulation, Ferroptosis, and Neurodegeneration
7.1. Regional Selectivity of Iron Accumulation and Neuronal Vulnerability
7.2. Ferroptosis Signatures in Alzheimer’s and Parkinson’s Disease
7.3. Iron, Protein Aggregation, and Liquid-Liquid Phase Separation (LLPS)
7.4. Mitochondrial ROS
7.5. Neuroinflammation and Ferroptosis
7.6. Aging and Ferroptosis Susceptibility
8. Iron Dyshomeostasis and Ferroptosis: Implications for Other Neurodegenerative Conditions
8.1. Amyotrophic Lateral Sclerosis (ALS)—Ferroptotic Motor Neuron Loss
8.2. Huntington’s Disease (HD)—Iron, Mitochondria, and Striatal Neurodegeneration
8.3. Multiple Sclerosis (MS)—Iron, Ferroptosis, and Demyelination
8.4. Converging Mechanisms: Iron-Mediated Ferroptosis as a Common Pathway in Neurodegeneration
9. Clinical Translation: Iron Chelation and Overcoming the Blood-Brain Barrier
10. Challenges and Future Directions
11. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Abdukarimov, N.; Kokabi, K.; Kunz, J. Ferroptosis and Iron Homeostasis: Molecular Mechanisms and Neurodegenerative Disease Implications. Antioxidants 2025, 14, 527. https://doi.org/10.3390/antiox14050527
Abdukarimov N, Kokabi K, Kunz J. Ferroptosis and Iron Homeostasis: Molecular Mechanisms and Neurodegenerative Disease Implications. Antioxidants. 2025; 14(5):527. https://doi.org/10.3390/antiox14050527
Chicago/Turabian StyleAbdukarimov, Nurzhan, Kamilya Kokabi, and Jeannette Kunz. 2025. "Ferroptosis and Iron Homeostasis: Molecular Mechanisms and Neurodegenerative Disease Implications" Antioxidants 14, no. 5: 527. https://doi.org/10.3390/antiox14050527
APA StyleAbdukarimov, N., Kokabi, K., & Kunz, J. (2025). Ferroptosis and Iron Homeostasis: Molecular Mechanisms and Neurodegenerative Disease Implications. Antioxidants, 14(5), 527. https://doi.org/10.3390/antiox14050527