Ferroptosis and Its Potential Role in the Nervous System Diseases

Zhou, Yiyang; Lin, Wei; Rao, T. Rajeswara; Zheng, Jinyu; Zhang, Tianlei; Zhang, Min; Lin, Zhenlang

doi:10.2147/jir.s351799

Cited by 46 publications

(30 citation statements)

References 185 publications

(226 reference statements)

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“…Moreover, previous reports have suggested that ischemia can result in iron accumulation within the acidulated environment, which, together with glutamate accumulation after HIBI, can inhibit system X C − and then induce ferroptosis 38,45 . Ferroptosis may be closely related to brain development, and genes associated with ferroptosis are highly expressed in the embryonic and postnatal brain 46 . Embryonically, the expression of ferroptosis‐related genes such as SLC7A11 and HMOX1 is increased, promoting nerve‐cell proliferation and cognitive development 47 .…”

Section: Discussionmentioning

confidence: 99%

“… 38 , 45 Ferroptosis may be closely related to brain development, and genes associated with ferroptosis are highly expressed in the embryonic and postnatal brain. 46 Embryonically, the expression of ferroptosis‐related genes such as SLC7A11 and HMOX1 is increased, promoting nerve‐cell proliferation and cognitive development. 47 In addition, iron is an essential nutrient for neurodevelopment in infants; however, excess iron accumulation is harmful to brain development.…”

Section: Discussionmentioning

confidence: 99%

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Ferroptosis contributes to hypoxic–ischemic brain injury in neonatal rats: Role of the SIRT1/Nrf2/GPx4 signaling pathway

Xue

et al. 2022

CNS Neurosci Ther

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Aims Hypoxic–ischemic brain injury (HIBI) often results in cognitive impairments. Herein, we investigated the roles of ferroptosis in HIBI and the underlying signaling pathways. Methods Ferrostatin‐1 (Fer‐1) or resveratrol (Res) treatments were administered intracerebroventricularly 30 min before HIBI in 7‐day‐old rats. Glutathione peroxidase 4 (GPx4) expression, malondialdehyde (MDA) concentration, iron content, mitochondrial morphology, and the expression of silent information regulator factor 2‐related enzyme 1 (SIRT1) and nuclear factor erythroid‐2‐related factor 2 (Nrf2) were measured after HIBI. Additionally, the weight ratio of left/right hemisphere, brain morphology, Nissl staining, and the Morris water maze test were conducted to estimate brain damage. Results At 24‐h post‐HIBI, GPx4 expression was decreased, and MDA concentration and iron content were increased in the hippocampus. HIBI led to mitochondrial atrophy, brain atrophy/damage, and resultant learning and memory impairments, which were alleviated by Fer‐1‐mediated inhibition of ferroptosis. Furthermore, Res‐mediated SIRT1 upregulation increased Nrf2 and GPx4 expression, thereby attenuating ferroptosis, reducing brain atrophy/damage, and improving learning and memory abilities. Conclusion The results demonstrated that during HIBI, ferroptosis occurs via the SIRT1/Nrf2/GPx4 signaling pathway, suggesting it as a potential therapeutic target for inhibiting ferroptosis and ameliorating HIBI‐induced cognitive impairments.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ferroptosis contributes to hypoxic–ischemic brain injury in neonatal rats: Role of the SIRT1/Nrf2/GPx4 signaling pathway

Xue

et al. 2022

CNS Neurosci Ther

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“…The mechanisms of iron metabolism in ferroptosis were displayed in Figure 2 . In addition to iron metabolism and lipid peroxidation responses, a wide range of intracellular antioxidant mechanisms also plays an important role in regulating ferroptosis sensitivity ( 63 , 64 ). Glutathione (GSH), the most important intracellular antioxidant metabolite, requires cysteine as a raw material for its synthesis, and cells can endogenously synthesize cysteine via the transsulfuration pathway to resist ferroptosis ( 65 , 66 ).…”

Section: Ferroptosismentioning

confidence: 99%

Ferroptosis, necroptosis, and pyroptosis in the occurrence and development of ovarian cancer

Zhang

Liu

2022

Front. Immunol.

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Ovarian cancer (OC) is one of the most common malignancies that causes death in women and is a heterogeneous disease with complex molecular and genetic changes. Because of the relatively high recurrence rate of OC, it is crucial to understand the associated mechanisms of drug resistance and to discover potential target for rational targeted therapy. Cell death is a genetically determined process. Active and orderly cell death is prevalent during the development of living organisms and plays a critical role in regulating life homeostasis. Ferroptosis, a novel type of cell death discovered in recent years, is distinct from apoptosis and necrosis and is mainly caused by the imbalance between the production and degradation of intracellular lipid reactive oxygen species triggered by increased iron content. Necroptosis is a regulated non-cysteine protease–dependent programmed cell necrosis, morphologically exhibiting the same features as necrosis and occurring via a unique mechanism of programmed cell death different from the apoptotic signaling pathway. Pyroptosis is a form of programmed cell death that is characterized by the formation of membrane pores and subsequent cell lysis as well as release of pro-inflammatory cell contents mediated by the abscisin family. Studies have shown that ferroptosis, necroptosis, and pyroptosis are involved in the development and progression of a variety of diseases, including tumors. In this review, we summarized the recent advances in ferroptosis, necroptosis, and pyroptosis in the occurrence, development, and therapeutic potential of OC.

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“…Ferroptosis is closely linked to the occurrence and development of neurodegenerative diseases, strokes, and brain tumors. It is also involved in the development, maturation, and aging of the nervous system ( 13 , 14 ). Many studies have found a link between ASD and elevated oxidative stress and ASD is contributed to by oxidative stress in several ways, including protein post-translational changes, abnormal metabolism (e.g., lipid peroxidation), and toxic buildup (e.g., ROS) ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Novel Diagnostic Model for Childhood Autism Spectrum Disorder Based on Ferroptosis-Related Genes

Qin

et al. 2022

Front. Psychiatry

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Autism spectrum disorder (ASD) is a highly genetic heterogeneous neurodevelopmental disorder, which is usually considered a heritable and heterogeneous neurodevelopmental disorder and has caused a great burden to society and families. Emerging roles of ferroptosis have been observed in neurological disorders. This study aimed to construct a diagnostic model based on ferroptosis-related genes (FRGs) to contribute to the early and precise diagnosis of childhood ASD. In the candidate FRGs, we identified 27 differentially expressed genes (DEGs) between ASD patients and typically developing (TD) controls. Four key FRGs were identified using the random forest analysis for further analysis. Utilization of the four gene expression, we constructed a diagnostic model and the AUC value in the training dataset (GSE18123) is 0.7002. We deem that a patient with a score less than 0.9904 is likely to have ASD. Three validation datasets (GSE111176, GSE113834, and GSE28521) were collected and the AUC value is 0.7442, 0.7444, and 0.6474, respectively. A multi-factor regulatory network based on four FRGs indicated that RORA, EAF1, NFYB, miR-4703-3p, and miR-6073 may play a role in the development of ASD. In addition, we found piperaquine may have the potential to be a promising drug for the treatment of ASD. Overall, we constructed a diagnostic model of childhood ASD, which could contribute to the precision diagnosis and timely treatment of childhood ASD.

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Ferroptosis and Its Potential Role in the Nervous System Diseases

Cited by 46 publications

References 185 publications

Ferroptosis contributes to hypoxic–ischemic brain injury in neonatal rats: Role of the SIRT1/Nrf2/GPx4 signaling pathway

Ferroptosis contributes to hypoxic–ischemic brain injury in neonatal rats: Role of the SIRT1/Nrf2/GPx4 signaling pathway

Ferroptosis, necroptosis, and pyroptosis in the occurrence and development of ovarian cancer

Development and Validation of a Novel Diagnostic Model for Childhood Autism Spectrum Disorder Based on Ferroptosis-Related Genes

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