The initiator of neuroexcitotoxicity and ferroptosis in ischemic stroke: Glutamate accumulation

Fan, Genhao; Liu, Meilin; Liu, Jia; Huang, Yü

doi:10.3389/fnmol.2023.1113081

Cited by 23 publications

(6 citation statements)

References 234 publications

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“…Following a stroke, two main areas are primarily affected: i) The infarct zone (where cell death occurs due to ischemia) ( 84 ); and ii) the surrounding ischemic penumbra ( 85 ). Alterations in glutamate are known to induce the occurrence of ferroptosis during a stroke, with a significant increase in extracellular glutamate levels released by neurons in these areas ( 86 ). Consequently, the balance between system Xc − and glutamate transport is disrupted, leading to both a reduced intracellular uptake of glutamate and an inhibition of GSH synthesis due to the lack of necessary raw materials ( 87 ).…”

Section: Ferroptosis-associated Pathways In Strokementioning

confidence: 99%

Recent advances in potential therapeutic targets of ferroptosis‑associated pathways for the treatment of stroke (Review)

Dong,

Ma,

Cui

et al. 2024

Mol Med Rep

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Stroke is a severe neurological disease that is associated with high rates of morbidity and mortality, and the underlying pathological processes are complex. Ferroptosis fulfills a significant role in the progression and treatment of stroke. It is well established that ferroptosis is a type of programmed cell death that is distinct from other forms or types of cell death. The process of ferroptosis involves multiple signaling pathways and regulatory mechanisms that interact with mechanisms inherent to stroke development. Inducers and inhibitors of ferroptosis have been shown to exert a role in the onset of this cell death process. Furthermore, it has been shown that interfering with ferroptosis affects the occurrence of stroke, indicating that targeting ferroptosis may offer a promising therapeutic approach for treating patients of stroke. Hence, the present review aimed to summarize the latest progress that has been made in terms of using therapeutic interventions for ferroptosis as treatment targets in cases of stroke. It provides an overview of the relevant pathways and molecular mechanisms that have been investigated in recent years, highlighting the roles of inducers and inhibitors of ferroptosis in stroke. Additionally, the intervention potential of various types of Traditional Chinese Medicine is also summarized. In conclusion, the present review provides a comprehensive overview of the potential therapeutic targets afforded by ferroptosis-associated pathways in stroke, offering new insights into how ferroptosis may be exploited in the treatment of stroke.

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Section: Ferroptosis-associated Pathways In Strokementioning

confidence: 99%

Recent advances in potential therapeutic targets of ferroptosis‑associated pathways for the treatment of stroke (Review)

Dong,

Ma,

Cui

et al. 2024

Mol Med Rep

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“…The cystine/glutamate transporter pathway also influences ferroptosis ( 19 – 21 ). In organotypic hippocampal culture models (OHSC), glutamate can trigger excitotoxic cell death by modulating calcium influx or inhibiting the cystine absorption pathway (system Xc-) ( 5 ).…”

Section: Key Mechanisms Of Ferroptosis: Unraveling the Pathways And S...mentioning

confidence: 99%

Role of mitochondria in the regulation of ferroptosis and disease

Fu,

Cao,

Zeng

et al. 2023

Front. Med.

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Ferroptosis is a distinctive form of iron-dependent cell death characterized by significant ultrastructural changes in mitochondria. Given the crucial involvement of mitochondria in various cellular processes such as reactive oxygen species production, energy metabolism, redox status, and iron metabolism, mounting evidence suggests a vital role of mitochondria in the regulation and execution of ferroptosis. Furthermore, there exists a strong correlation between ferroptosis and various diseases. In this review, we aim to summarize the mechanisms underlying the induction and defense of ferroptosis, emphasizing the influence of mitochondria on this intricate process. Additionally, we provide an overview of the role of ferroptosis in disease, particularly cancer, and elucidate the mechanisms by which drugs targeting mitochondria impact ferroptosis. By presenting a theoretical foundation and reference point, this review aims to contribute to both basic cell biology research and the investigation of clinically relevant diseases.

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“…NRF2 can promote SLC7A11 expression, and knocking down NRF2 promotes the occurrence of ferroptosis (Dong et al, 2020). Additionally, as the extracellular concentration of glutamate increases, it can inhibit system x c -, thereby inducing ferroptosis, which indicates that glutamate is also a regulatory factor in ferroptosis (Fan et al, 2023).…”

Section: Amino Acid Metabolism and Ferroptosismentioning

confidence: 99%

The role of ferroptosis in diabetic cardiovascular diseases and the intervention of active ingredients of traditional Chinese medicine

Zhang,

Sun,

Wang

et al. 2023

Front. Pharmacol.

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Cardiovascular diseases (CVDs), encompassing ischaemic heart disease, cardiomyopathy, and heart failure, among others, are the most prevalent complications of diabetes and the leading cause of mortality in patients with diabetes. Cell death modalities, including apoptosis, necroptosis, and pyroptosis, have been demonstrated to be involved in the pathogenesis of CVDs. As research progresses, accumulating evidence also suggests the involvement of ferroptosis, a novel form of cell death, in the pathogenesis of CVDs. Ferroptosis, characterised by iron-dependent lipid peroxidation, which culminates in membrane rupture, may present new therapeutic targets for diabetes-related cardiovascular complications. Current treatments for CVDs, such as antihypertensive, anticoagulant, lipid-lowering, and plaque-stabilising drugs, may cause severe side effects with long-term use. Traditional Chinese medicine, with its broad range of activities and minimal side effects, is widely used in China. Numerous studies have shown that active components of Chinese medicine, such as alkaloids, polyphenols, and saponins, can prevent CVDs by regulating ferroptosis. This review summarises the recent findings on the regulatory mechanisms of active components of Chinese medicine against ferroptosis in CVDs, aiming to provide new directions and a scientific basis for targeting ferroptosis for the prevention and treatment of diabetic CVDs.

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The initiator of neuroexcitotoxicity and ferroptosis in ischemic stroke: Glutamate accumulation

Cited by 23 publications

References 234 publications

Recent advances in potential therapeutic targets of ferroptosis‑associated pathways for the treatment of stroke (Review)

Recent advances in potential therapeutic targets of ferroptosis‑associated pathways for the treatment of stroke (Review)

Role of mitochondria in the regulation of ferroptosis and disease

The role of ferroptosis in diabetic cardiovascular diseases and the intervention of active ingredients of traditional Chinese medicine

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