Oxytosis/Ferroptosis in Neurodegeneration: the Underlying Role of Master Regulator Glutathione Peroxidase 4 (GPX4)

Dar, Nawab John; John, Urmilla; Bano, Nargis; Khan, Sameera; Bhat, Shahnawaz Ali

doi:10.1007/s12035-023-03646-8

Cited by 18 publications

(7 citation statements)

References 179 publications

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“…These toxic lipid peroxides can be reduced to lipid alcohols (L-OH) by GSH and GPX4, and the system Xc − is a key regulator of GSH synthesis, and solute carrier family 3 member 2 (SLC3A2) and solute carrier family 7 member 11 (SLC7A11) are major components of this transporter. System Xc − and GPX4 are therefore important targets for the regulation of ferroptosis, and when their metabolism is imbalanced, lipid peroxidation is unchecked, leading to ferroptosis ( Dar et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Research trends of ferroptosis and pyroptosis in Parkinson’s disease: a bibliometric analysis

Wu,

Zhong,

Tang

et al. 2024

Front. Mol. Neurosci.

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ObjectiveThis study aims to visualize the trends and hotspots in the research of “ferroptosis in PD” and “pyroptosis in PD” through bibliometric analysis from the past to 2024.MethodsLiterature was retrieved from the Web of Science Core Collection (WoSCC) from the past to February 16, 2024, and bibliometric analysis was conducted using Vosviewer and Citespace.Results283 and 542 papers were collected in the field of “ferroptosis in PD” and “pyroptosis in PD.” The number of publications in both fields has increased yearly, especially in “ferroptosis in PD,” which will become the focus of PD research. China, the United States and England had extensive exchanges and collaborations in both fields, and more than 60% of the top 10 institutions were from China. In the fields of “ferroptosis in PD” and “pyroptosis in PD,” the University of Melbourne and Nanjing Medical University stood out in terms of publication numbers, citation frequency, and centrality, and the most influential journals were Cell and Nature, respectively. The keyword time zone map showed that molecular mechanisms and neurons were the research hotspots of “ferroptosis in PD” in 2023, while memory and receptor 2 were the research hotspots of “pyroptosis in PD” in 2023, which may predict the future research direction.ConclusionThis study provides insights into the development, collaborations, research themes, hotspots, and tendencies of “ferroptosis in PD” and “pyroptosis in PD.” Overall situation of these fields is available for researchers to further explore the underlying mechanisms and potential treatments.

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Section: Discussionmentioning

confidence: 99%

Research trends of ferroptosis and pyroptosis in Parkinson’s disease: a bibliometric analysis

Wu,

Zhong,

Tang

et al. 2024

Front. Mol. Neurosci.

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“…System Xc-passes through a heterodimer of the light-chain subunit SLC7A11 and the heavy-chain subunit SLC3A2, and glutamate-cysteine ligase (GCL) and glutathione synthase (GSS) transfer cystine to the cell and synthesise glutathione (GSH). Then, GSH is converted to Oxidized glutathione (GSSG) with the participation of glutathione peroxidation GPX4 to eliminate toxic lipid peroxides ( Dar et al, 2024 ). Moreover, in the presence of GSH GPX4 converts toxic lipid peroxides into non-toxic lipocalciferol, which protects cells from lipid peroxidation and thus inhibits ferroptosis ( Dar et al, 2024 ).…”

Section: Small Molecule Ferroptosis Inhibitorsmentioning

confidence: 99%

“…Then, GSH is converted to Oxidized glutathione (GSSG) with the participation of glutathione peroxidation GPX4 to eliminate toxic lipid peroxides ( Dar et al, 2024 ). Moreover, in the presence of GSH GPX4 converts toxic lipid peroxides into non-toxic lipocalciferol, which protects cells from lipid peroxidation and thus inhibits ferroptosis ( Dar et al, 2024 ).…”

Section: Small Molecule Ferroptosis Inhibitorsmentioning

confidence: 99%

Ferroptosis inhibitors: past, present and future

Zhang,

Luo,

Xiang

et al. 2024

Front. Pharmacol.

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Ferroptosis is a non-apoptotic mode of programmed cell death characterized by iron dependence and lipid peroxidation. Since the ferroptosis was proposed, researchers have revealed the mechanisms of its formation and continue to explore effective inhibitors of ferroptosis in disease. Recent studies have shown a correlation between ferroptosis and the pathological mechanisms of neurodegenerative diseases, as well as diseases involving tissue or organ damage. Acting on ferroptosis-related targets may provide new strategies for the treatment of ferroptosis-mediated diseases. This article specifically describes the metabolic pathways of ferroptosis and summarizes the reported mechanisms of action of natural and synthetic small molecule inhibitors of ferroptosis and their efficacy in disease. The paper also describes ferroptosis treatments such as gene therapy, cell therapy, and nanotechnology, and summarises the challenges encountered in the clinical translation of ferroptosis inhibitors. Finally, the relationship between ferroptosis and other modes of cell death is discussed, hopefully paving the way for future drug design and discovery.

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“…The critical phases involved in ferroptosis include the accumulation of intracellular free iron, glutathione depletion, and peroxidation of PUFA-rich membranes [82,83]. Recent evidence has documented ferroptosis as a crucial factor in the pathogenesis of several diseases, such as ND [82][83][84][85]. Accordingly, iron homeostasis, oxidative stress, and subsequent neuroinflammation have been described to contribute to the regulation of ferroptosis and neuronal health [82][83][84][85].…”

Section: Ferroptosis In Neuroinflammationmentioning

confidence: 99%

“…Recent evidence has documented ferroptosis as a crucial factor in the pathogenesis of several diseases, such as ND [82][83][84][85]. Accordingly, iron homeostasis, oxidative stress, and subsequent neuroinflammation have been described to contribute to the regulation of ferroptosis and neuronal health [82][83][84][85]. However, the precise molecular mechanisms underlying the involvement of ferroptosis in the pathological processes of neurodegeneration and its impact on neuronal dysfunction remain to be discovered.…”

Section: Ferroptosis In Neuroinflammationmentioning

confidence: 99%

Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

Balistreri,

Monastero

2023

Brain Sciences

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The term “neuroinflammation” defines the typical inflammatory response of the brain closely related to the onset of many neurodegenerative diseases (NDs). Neuroinflammation is well known, but its mechanisms and pathways are not entirely comprehended. Some progresses have been achieved through many efforts and research. Consequently, new cellular and molecular mechanisms, diverse and conventional, are emerging. In listing some of those that will be the subject of our description and discussion, essential are the important roles of peripheral and infiltrated monocytes and clonotypic cells, alterations in the gut–brain axis, dysregulation of the apelinergic system, alterations in the endothelial glycocalyx of the endothelial component of neuronal vascular units, variations in expression of some genes and levels of the encoding molecules by the action of microRNAs (miRNAs), or other epigenetic factors and distinctive transcriptional factors, as well as the role of autophagy, ferroptosis, sex differences, and modifications in the circadian cycle. Such mechanisms can add significantly to understanding the complex etiological puzzle of neuroinflammation and ND. In addition, they could represent biomarkers and targets of ND, which is increasing in the elderly.

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Oxytosis/Ferroptosis in Neurodegeneration: the Underlying Role of Master Regulator Glutathione Peroxidase 4 (GPX4)

Cited by 18 publications

References 179 publications

Research trends of ferroptosis and pyroptosis in Parkinson’s disease: a bibliometric analysis

Research trends of ferroptosis and pyroptosis in Parkinson’s disease: a bibliometric analysis

Ferroptosis inhibitors: past, present and future

Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

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