The DOI matches its Crossref record; 235 of the 235 references it cites were found in a registry or an index.
Striking while the iron is hot: Iron metabolism and ferroptosis in neurodegeneration
Open accessAbstract
ABSTRACT Perturbations in iron homeostasis and iron accumulation feature in several neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). Proteins such as &agr;‐synuclein, tau and amyloid precursor protein that are pathologically associated with neurodegeneration are involved in molecular crosstalk with iron homeostatic proteins. Quantitative susceptibility mapping, an MRI based non‐invasive technique, offers proximal evaluations of iron load in regions of the brain and powerfully predicts cognitive decline. Further, small molecules that target elevated iron have shown promise against PD and AD in preclinical studies and clinical trials. Despite these strong links between altered iron homeostasis and neurodegeneration the molecular biology to describe the association between enhanced iron levels and neuron death, synaptic impairment and cognitive decline is ill defined. In this review we discuss the current understanding of brain iron homeostasis and how it may be perturbed under pathological conditions. Further, we explore the ramifications of a novel cell death pathway called ferroptosis that has provided a fresh impetus to the “metal hypothesis” of neurodegeneration. While lipid peroxidation plays a central role in the execution of this cell death modality the removal of iron through chelation or genetic modifications appears to extinguish the ferroptotic pathway. Conversely, tissues that harbour elevated iron may be predisposed to ferroptotic damage. These emerging findings are of relevance to neurodegeneration where ferroptotic signalling may offer new targets to mitigate cell death and dysfunction. Graphical abstract Figure. No Caption available. HighlightsIron accumulation is a feature of several neurodegenerative disorders.Ferroptosis is a novel regulated cell death modality dependent on iron and lipid peroxidation.Growing evidence implicates ferroptosis in neurodegenerative disease.Iron chelation or small molecule anti‐ferroptotic agents may be neurotherapeutics.
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Cited by
Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis
Su, L.-J., Zhang, J.-H., Gomez, H., Murugan, R., Hong, X., Xu, D., Jiang, F., & Peng, Z.-Y. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/5080843 · Cited by 2,166
Ferroptosis and its potential role in the physiopathology of Parkinson’s Disease
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Self-citationInhibiting Ferroptosis through Disrupting the NCOA4–FTH1 Interaction: A New Mechanism of Action
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Molecular mechanisms of ferroptosis and their involvement in brain diseases
Costa, I., Barbosa, D. J., Benfeito, S., Silva, V., Chavarria, D., Borges, F., Remião, F., & Silva, R. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108373 · Cited by 402
Zhang, X., Sui, S., Wang, L., Li, H., Zhang, L., Xu, S., & Zheng, X. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29232 · Cited by 293
Metadata
- Authors
- Masaldan, S., Bush, A. I., Devos, D., Rolland, A. S., & Moreau, C.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 133
- Pages
- 221-233
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2894231856
- Cited by
- 481
- References
- 235
- FWCI
- 15.36
- Type
- journal article
- Language
- en
- Open access
- green
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- Masaldan, S., Bush, A. I., Devos, D., Rolland, A. S., & Moreau, C. (2019). Striking while the iron is hot: Iron metabolism and ferroptosis in neurodegeneration. Free Radical Biology and Medicine. https://doi.org/10.1016/j.freeradbiomed.2018.09.033
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