Targeting iNOS Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage via Promoting Ferroptosis of M1 Microglia and Reducing Neuroinflammation

Qu, Wenhao; Cheng, Ying; Peng, Wei; Wu, Yan; Rui, Tongyu; Luo, Chengliang; Zhang, Jian

doi:10.1007/s12035-022-02788-5

Cited by 36 publications

(26 citation statements)

References 46 publications

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“…Given that, ferroptotic factors and ferroptosis-related signaling pathways have now been considered as potential diagnostic/prognostic biomarkers and therapeutic targets of NDDs. It is also worth-noting that ferroptosis has been reported to participate in neuroinflammation and neuronal death post-acute brain damage, which may play a role in the pathogenesis of NDDs as well ( Mao et al, 2020 ; Cao et al, 2021 ; Cui et al, 2021 ; Ge et al, 2022 ; Qu et al, 2022 ).…”

Section: Emerging Links Of Ferroptosis To Neurodegenerative Diseasesmentioning

confidence: 99%

Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases

Sun

Xia

Basnet

et al. 2022

Front. Aging Neurosci.

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Neurodegenerative diseases are a diverse class of diseases attributed to chronic progressive neuronal degeneration and synaptic loss in the brain and/or spinal cord, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and multiple sclerosis. The pathogenesis of neurodegenerative diseases is complex and diverse, often involving mitochondrial dysfunction, neuroinflammation, and epigenetic changes. However, the pathogenesis of neurodegenerative diseases has not been fully elucidated. Recently, accumulating evidence revealed that ferroptosis, a newly discovered iron-dependent and lipid peroxidation-driven type of programmed cell death, provides another explanation for the occurrence and progression of neurodegenerative diseases. Here, we provide an overview of the process and regulation mechanisms of ferroptosis, and summarize current research progresses that support the contribution of ferroptosis to the pathogenesis of neurodegenerative diseases. A comprehensive understanding of the emerging roles of ferroptosis in neurodegenerative diseases will shed light on the development of novel therapeutic technologies and strategies for slowing down the progression of these diseases.

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Section: Emerging Links Of Ferroptosis To Neurodegenerative Diseasesmentioning

confidence: 99%

Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases

Sun

Xia

Basnet

et al. 2022

Front. Aging Neurosci.

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“…Hence, oxidative stress has become a critical linking between ferroptosis and neurological disorders. Up to now, the inhibitors and activators of ferroptosis [9][10][11][12][13][14], as well as other involved signaling pathways [15][16][17], have been widely studied. Furthermore, the mediators of oxidative stress might become a potential therapeutic target for the treatment of neurological disorders by regulating the process of ferroptosis.…”

Section: Introductionmentioning

confidence: 99%

Targeting Molecular Mediators of Ferroptosis and Oxidative Stress for Neurological Disorders

Jia

Cheng

et al. 2022

Oxidative Medicine and Cellular Longevity

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With the acceleration of population aging, nervous system diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), anxiety, depression, stroke, and traumatic brain injury (TBI) have become a huge burden on families and society. The mechanism of neurological disorders is complex, which also lacks effective treatment, so relevant research is required to solve these problems urgently. Given that oxidative stress-induced lipid peroxidation eventually leads to ferroptosis, both oxidative stress and ferroptosis are important mechanisms causing neurological disorders, targeting mediators of oxidative stress and ferroptosis have become a hot research direction at present. Our review provides a current view of the mechanisms underlying ferroptosis and oxidative stress participate in neurological disorders, the potential application of molecular mediators targeting ferroptosis and oxidative stress in neurological disorders. The target of molecular mediators or agents of oxidative stress and ferroptosis associated with neurological disorders, such as reactive oxygen species (ROS), nuclear factor erythroid 2–related factor-antioxidant response element (Nrf2-ARE), n-acetylcysteine (NAC), Fe2+, NADPH, and its oxidases NOX, has been described in this article. Given that oxidative stress-induced ferroptosis plays a pivotal role in neurological disorders, further research on the mechanisms of ferroptosis caused by oxidative stress will help provide new targets for the treatment of neurological disorders.

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“…Iron deposition by macrophages can lead to neuronal damage due to oxidative stress, free radical formation, and the promotion of pro-inflammatory mediators [54]. Macrophages that accumulate iron show an increase in TNF-α, which could contribute to the neuroinflammation observed in SAH [55, 56]. Indeed, inflammatory cytokines like TNF-α and IL-6 induce the expression of iron transporter receptors and promote the accumulation of iron in neurons and microglia (Fig.…”

Section: Iron Uptake In the Brainmentioning

confidence: 99%

Ferritin and Neurotoxicity: A Contributor to Deleterious Outcomes for Subarachnoid Hemorrhage

Panther

Zelmanovich²,

Hernandez

et al. 2022

Eur Neurol

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Background: Ferritin is a protein that is critical for storing iron. Ferritin has recently been shown to play a role in iron homeostasis, immunomodulation, inflammation, and antioxidation. Previously, it was believed that ferritin was exclusively an intracellular peptide. However, there is significant evidence that ferritin is also in the serum, cerebral spinal fluid, and synovial fluid. Summary: Within the brain, ferritin can bind to oligodendrocytes adjacent to the blood-brain barrier to allow a docking point for ferritin to be engulfed by microglia in the brain parenchyma. When iron supplies in the brain are low, the lysosomal-autophagy pathway is activated to degrade ferritin and mobilize iron. Iron is critical in the brain for the formation of myelin and used during cellular respiration. If this sequestration and degradation of iron are impaired, the oxidative effects of iron may leave the brain vulnerable to neurotoxic effects. Subarachnoid hemorrhage (SAH) causes hemolysis of erythrocytes leading to the release of iron. Subsequently, a rise in ferritin is observed which promotes the neurologic insult following SAH. The degree to which ferritin is elevated post-SAH may correlate with the downstream neurotoxicity. Key Messages: The literature seems to point to a critical balance in ferritin levels. Ferritin is protective against further oxidative effects of iron, but ferritin also contributes to neurotoxic outcomes. In this review, we will discuss the role of ferritin in the brain. Specifically, we will address cerebral ferritin iron uptake and ferritin clearance. This homeostatic process influences the development and progression of SAH.

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Targeting iNOS Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage via Promoting Ferroptosis of M1 Microglia and Reducing Neuroinflammation

Cited by 36 publications

References 46 publications

Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases

Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases

Targeting Molecular Mediators of Ferroptosis and Oxidative Stress for Neurological Disorders

Ferritin and Neurotoxicity: A Contributor to Deleterious Outcomes for Subarachnoid Hemorrhage

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