Molecular mechanisms of ferroptosis and their involvement in brain diseases
Open accessAbstract
Ferroptosis is a type of regulated cell death characterized by intracellular accumulation of iron and reactive oxygen species, inhibition of system Xc-, glutathione depletion, nicotinamide adenine dinucleotide phosphate oxidation and lipid peroxidation. Since its discovery and characterization in 2012, many efforts have been made to reveal the underlying mechanisms, modulating compounds, and its involvement in disease pathways. Ferroptosis inducers include erastin, sorafenib, sulfasalazine and glutamate, which, by inhibiting system Xc-, prevent the import of cysteine into the cells. RSL3, statins, Ml162 and Ml210 induce ferroptosis by inhibiting glutathione peroxidase 4 (GPX4), which is responsible for preventing the formation of lipid peroxides, and FIN56 and withaferin trigger GPX4 degradation. On the other side, ferroptosis inhibitors include ferrostatin-1, liproxstatin-1, α-tocopherol, zileuton, FSP1, CoQ10 and BH4, which interrupt the lipid peroxidation cascade. Additionally, deferoxamine, deferiprone and N-acetylcysteine, by targeting other cellular pathways, have also been classified as ferroptosis inhibitors. Increased evidence has established the involvement of ferroptosis in distinct brain diseases, including Alzheimer's, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, multiple sclerosis, and Friedreich's ataxia. Thus, a deep understanding of how ferroptosis contributes to these diseases, and how it can be modulated, can open a new window of op…
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Deferoxamine is a well-established iron chelator that inhibits LPO and ferroptosis in several experimental models of brain diseases.
“We also investigated effect of deferoxamine, a well-established iron chelator, which was shown to inhibit LPO and ferroptosis in several experimental models of brain diseases (Costa et al., 2023).”
From Toxic Concentrations of Glutamate Induce Ferroptosis without Affecting Mitochondrial Respiration in Rodent Brain Slice Cultures (2026) · cites this paper as Costa et al., 2023
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- Authors
- Costa, I., Barbosa, D. J., Benfeito, S., Silva, V., Chavarria, D., Borges, F., Remião, F., & Silva, R.
- Affiliations
- Universidade do Porto (PT)
- Corresponding author
- Costa, Inês
- Benfeito, Sofia
- Silva, Renata
- ORCID
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2023-04
- Volume
- 244
- Pages
- 108373
- ISSN
- 0163-7258 (ISSN-L)
- OpenAlex
- W4323349858
- Cited by
- 402
- References
- 29
- Citations by year
- 2026: 114 · 2025: 154 · 2024: 104 · 2023: 30
- FWCI
- 17.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Pharmacology & Therapeutics (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Fundação para a Ciência e a Tecnologia (UIDB/00081/2020, LA/P/0140/2020, UIDB/04378/2020, LA/P/0056/2020, UIDP/04378/2020)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- ferroptosis, regulated cell death, brain disorders, lipid peroxidation, system xc-, GPX4, ferroptosis inducers, ferroptosis inhibitors, erastin, RSL3, statins, glutamate, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, Friedreich's ataxia, RAS mutations, brain tumors
- MeSH terms
- Ferroptosis, Brain Diseases, Humans, Lipid Peroxidation, Cell Death, Reactive Oxygen Species
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