Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications

Stockwell, Brent R.

doi:10.1016/j.cell.2022.06.003

Cited by 945 publications

(821 citation statements)

References 156 publications

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“…In addition to oxygen transport, iron also has a vital role in many metabolic processes with the potential to cause oxidative damage when in excess ( 1 ). Specifically, serum ferric iron is carried by transferrin and transported into the cell, where it is reduced to ferrous iron ( 2 ). Ferrous iron facilitates peroxidation of membrane-bound, PUFA-containing lipids and triggers propagation of lipid peroxidation, which cause damage to mitochondria and other organelles and finally lead to the development and progression of metabolic disorders ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, serum ferric iron is carried by transferrin and transported into the cell, where it is reduced to ferrous iron ( 2 ). Ferrous iron facilitates peroxidation of membrane-bound, PUFA-containing lipids and triggers propagation of lipid peroxidation, which cause damage to mitochondria and other organelles and finally lead to the development and progression of metabolic disorders ( 2 ). Therefore, iron overload may be linked to multiple metabolic disorders such as obesity, hyperlipidemia, hyperglycemia, and insulin resistance ( 1 , 3 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

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Serum iron is closely associated with metabolic dysfunction-associated fatty liver disease in type 2 diabetes: A real-world study

Wang

Jin

et al. 2022

Front. Endocrinol.

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AimsThere is still a debate about the relationship between serum iron and metabolic dysfunction-associated fatty liver disease (MAFLD). Furthermore, few relevant studies were conducted in type 2 diabetes mellitus (T2DM). Therefore, this study aimed to explore the association of serum iron levels with MAFLD in Chinese patients with T2DM.MethodsThis cross-sectional, real-world study consisted of 1,467 Chinese T2DM patients. MAFLD was diagnosed by abdominal ultrasonography. Based on serum iron quartiles, the patients were classified into four groups. Clinical characteristics were compared among the four groups, and binary logistic analyses were used to assess the associations of serum iron levels and quartiles with the presence of MAFLD in T2DM.ResultsAfter adjusting for gender, age, and diabetes duration, significantly higher prevalence of MAFLD was found in the second (45.7%), third (45.2%), and fourth (47.0%) serum iron quartiles than in the first quartiles (26.8%), with the highest MAFLD prevalence in the fourth quartile (p < 0.001 for trend). Moreover, increased HOMA2-IR (p = 0.003 for trend) and decreased HOMA2-S (p = 0.003 for trend) were observed across the serum iron quartiles. Fully adjusted binary logistic regression analyses indicated that both increased serum iron levels (OR: 1.725, 95% CI: 1.427 to 2.085, p < 0.001) and quartiles (p < 0.001 for trend) were still closely associated with the presence of MAFLD in T2DM patients even after controlling for multiple confounding factors.ConclusionsThere is a positive correlation between the presence of MAFLD and serum iron levels in T2DM patients, which may be attributed to the close association between serum iron and insulin resistance. Serum iron levels may act as one of the indicators for evaluating the risk of MAFLD in T2DM individuals.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum iron is closely associated with metabolic dysfunction-associated fatty liver disease in type 2 diabetes: A real-world study

Wang

Jin

et al. 2022

Front. Endocrinol.

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“…Concerning its role in neurodegeneration, Lf seems to be increased around amyloid plaques in post-mortem Alzheimer’s disease (AD) brains [ 171 ] and in APP-transgenic mice (specially in animals older than 20 months), which resemble the later stages of AD [ 172 ]. The purpose of this accumulation around amyloid deposits remains unknown; recently, the APOE ε4 allele [ 183 ], which is strongly related to the onset of AD, has been related to abnormalities in brain iron homeostasis and the induction of ferroptosis [ 183 , 184 ]. In this paper, although lactoferrin was not mentioned, other transferrins were studied.…”

Section: Lactoferrin For Preventing Neurodegeneration: a Promising Mo...mentioning

confidence: 99%

Neuroprotective Role of Lactoferrin during Early Brain Development and Injury through Lifespan

2022

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Early adverse fetal environments can significantly disturb central nervous system (CNS) development and subsequently alter brain maturation. Nutritional status is a major variable to be considered during development and increasing evidence links neonate and preterm infant impaired brain growth with neurological and psychiatric diseases in adulthood. Breastfeeding is one of the main components required for healthy newborn development due to the many “constitutive” elements breastmilk contains. Maternal intake of specific nutrients during lactation may alter milk composition, thus affecting newborn nutrition and, potentially, brain development. Lactoferrin (Lf) is a major protein present in colostrum and the main protein in human milk, which plays an important role in the benefits of breastfeeding during postnatal development. It has been demonstrated that Lf has antimicrobial, as well as anti-inflammatory properties, and is potentially able to reduce the incidence of sepsis and necrotizing enterocolitis (NEC), which are particularly frequent in premature births. The anti-inflammatory effects of Lf can reduce birth-related pathologies by decreasing the release of pro-inflammatory factors and inhibiting premature cervix maturation (also related to commensal microbiome abnormalities) that could contribute to disrupting brain development. Pre-clinical evidence shows that Lf protects the developing brain from neuronal injury, enhances brain connectivity and neurotrophin production, and decreases inflammation in models of perinatal inflammatory challenge, intrauterine growth restriction (IUGR) and neonatal hypoxia-ischemia (HI). In this context, Lf can provide nutritional support for brain development and cognition and prevent the origin of neuropsychiatric diseases later in life. In this narrative review, we consider the role of certain nutrients during neurodevelopment linking to the latest research on lactoferrin with respect to neonatology. We also discuss new evidence indicating that early neuroprotective pathways modulated by Lf could prevent neurodegeneration through anti-inflammatory and immunomodulatory processes.

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“…6 Ferroptosis is a non-apoptotic form of RCD characterized by excessive iron-dependent lipid peroxidation (LPO). 7 In 2003, Brent R. Stockwell's group found that the oncogenic RASselective lethal small molecule erastin could selectively kill genetically-engineered human foreskin fibroblasts expressing an oncogenic mutant HRAS (HRas proto-oncogene, GTPase). 8 His group later identified that RAS-selective-lethal-3 (RSL3) could also induce nonapoptotic and iron-dependent oxidative cell death in 2008.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in small-molecule fluorescent probes for studying ferroptosis

Wang

Chen

et al. 2022

Chem. Soc. Rev.

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Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications

Cited by 945 publications

References 156 publications

Serum iron is closely associated with metabolic dysfunction-associated fatty liver disease in type 2 diabetes: A real-world study

Serum iron is closely associated with metabolic dysfunction-associated fatty liver disease in type 2 diabetes: A real-world study

Neuroprotective Role of Lactoferrin during Early Brain Development and Injury through Lifespan

Recent advances in small-molecule fluorescent probes for studying ferroptosis

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