Nrf2 Regulates Oxidative Stress and Its Role in Cerebral Ischemic Stroke

Antioxidants, Journal Year: 2022, Volume and Issue: 11(12), P. 2377 - 2377

Published: Nov. 30, 2022

Cerebral ischemic stroke is characterized by acute ischemia in a certain part of the brain, which leads to brain cells necrosis, apoptosis, ferroptosis, pyroptosis, etc. At present, there are limited effective clinical treatments for cerebral stroke, and recovery blood circulation will lead ischemia-reperfusion injury (CIRI). involves many pathological processes such as oxidative stress, inflammation, mitochondrial dysfunction. Nuclear factor erythroid 2-related 2 (Nrf2), one most critical antioxidant transcription factors cells, can coordinate various cytoprotective inhibit stress. Targeting Nrf2 considered potential strategy prevent treat injury. During ischemia, participates signaling pathways Keap1, PI3K/AKT, MAPK, NF-κB, HO-1, then alleviates or CIRI inhibiting anti-inflammation, maintaining homeostasis, protecting blood–brain barrier, ferroptosis. In this review, we have discussed structure Nrf2, mechanisms related research on treatment through pathway recent years, expounded important role future stroke.

Language: Английский

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ROS induced lipid peroxidation and their role in ferroptosis

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Aug. 1, 2023

Reactive oxygen species (ROS) play a crucial part in the process of cell death, including apoptosis, autophagy, and ferroptosis. ROS involves oxidation lipids generate 4-hydroxynonenal other compounds associated with it. Ferroptosis may be facilitated by lipid peroxidation phospholipid bilayers. In order to offer novel ideas directions for investigation disorders connected these processes, we evaluate function which ultimately leads ferroptosis as well proposed crosstalk mechanisms between types programmed death.

Language: Английский

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Molecular mechanisms of ferroptosis and relevance to inflammation

Inflammation Research, Journal Year: 2022, Volume and Issue: 72(2), P. 281 - 299

Published: Dec. 19, 2022

Language: Английский

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Targeting ferroptosis in acute kidney injury

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(2)

Published: Feb. 24, 2022

Acute kidney injury (AKI) is a major public health problem with high incidence and mortality. As form of programmed cell death (PCD), ferroptosis could be considered as process iron accumulation enhanced lipid peroxidation. Recently, the fundamental roles in AKI have attracted much attention. The network mechanism its to chronic disease (CKD) transition complicated multifactorial. Strategies targeting show great potential. Here, we review research progress on participation AKI. We hope that this work will provide clues for further studies

Language: Английский

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Alzheimer’s disease: Insights and new prospects in disease pathophysiology, biomarkers and disease-modifying drugs

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 211, P. 115522 - 115522

Published: March 28, 2023

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases that affect millions people worldwide, with both prevalence and incidence increasing age. It characterized by cognitive decline associated, specifically, degeneration cholinergic neurons. The problem this even more fundamental as available therapies remain fairly limited mainly focused on symptoms' relief. Although aetiology remains elusive, two main pathological hallmarks are described: i) presence neurofibrillary tangles formed unfolded protein aggregates (hyperphosphorylated Tau protein) ii) extracellular amyloid-beta peptide. Given complexity surrounding pathogenesis disease, several potential targets have been highlighted interrelated upon its progression, such oxidative stress accumulation metal ions. Thus, advances made development innovative multitarget therapeutical compounds to delay progression restore cell function. This review focuses ongoing research new insights emerging disease-modifying drugs for AD treatment. Furthermore, classical novel biomarkers early diagnosis their role in assisting improvement targeted will also be approached.

Language: Английский

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Autophagy, Pyroptosis, and Ferroptosis: New Regulatory Mechanisms for Atherosclerosis

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 9

Published: Jan. 13, 2022

Atherosclerosis is a chronic inflammatory disorder characterized by the gradual buildup of plaques within vessel wall middle-sized and large arteries. The occurrence development atherosclerosis rupture are related to injury vascular cells, including endothelial smooth muscle macrophages. Autophagy subcellular process that plays an important role in degradation proteins damaged organelles, autophagy cells closely atherosclerosis. Pyroptosis proinflammatory form regulated cell death, while ferroptosis nonapoptotic death involving overwhelming iron-dependent lipid peroxidation. Both them exhibit distinct features from apoptosis, necrosis, morphology, biochemistry, genetics. However, growing body evidence suggests pyroptosis interact with participate cancers, degenerative brain diseases cardiovascular diseases. This review updated current understanding autophagy, pyroptosis, ferroptosis, finding potential links their effects on atherogenesis plaque stability, thus providing ways develop new pharmacological strategies address stabilize vulnerable, ruptured plaques.

Language: Английский

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Autophagy mediates an amplification loop during ferroptosis

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(7)

Published: July 25, 2023

Ferroptosis, a programmed cell death, has been identified and associated with cancer various other diseases. Ferroptosis is defined as reactive oxygen species (ROS)-dependent death related to iron accumulation lipid peroxidation, which different from apoptosis, necrosis, autophagy, forms of death. However, accumulating evidence revealed link between autophagy ferroptosis at the molecular level suggested that involved in regulating iron-dependent peroxidation ROS during ferroptosis. Understanding roles pathophysiological processes may provide effective strategies for treatment ferroptosis-related In this review, we summarize current knowledge regarding regulatory mechanisms underlying ferroptosis, including metabolism, its association pathway. addition, discuss contribution elucidate role enhancer ROS-dependent

Language: Английский

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Oxidative stress in intervertebral disc degeneration: Molecular mechanisms, pathogenesis and treatment

Cell Proliferation, Journal Year: 2023, Volume and Issue: 56(9)

Published: March 13, 2023

Abstract Low back pain (LBP) is a leading cause of labour loss and disability worldwide, it also imposes severe economic burden on patients society. Among symptomatic LBP, approximately 40% caused by intervertebral disc degeneration (IDD). IDD the pathological basis many spinal degenerative diseases such as herniation stenosis. Currently, therapeutic approaches for mainly include conservative treatment surgical treatment, neither which can solve problem from root terminating process (IVD). Therefore, further exploring pathogenic mechanisms adopting targeted strategies one current research hotspots. complex pathophysiological processes IDD, oxidative stress considered main factor. The delicate balance between reactive oxygen species (ROS) antioxidants essential maintaining normal function survival IVD cells. Excessive ROS levels damage to macromolecules nucleic acids, lipids, proteins cells, affect cellular activities functions, ultimately lead cell senescence or death. This review discusses potential role in understand provides IDD.

Language: Английский

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High Level of Uric Acid Promotes Atherosclerosis by Targeting NRF2-Mediated Autophagy Dysfunction and Ferroptosis

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 21

Published: April 18, 2022

Atherosclerotic vascular disease (ASVD) is the leading cause of death worldwide. Hyperuricemia fourth risk factor for atherosclerosis after hypertension, diabetes, and hyperlipidemia. The mechanism hyperuricemia affecting occurrence development has not been fully elucidated. Mononuclear macrophages play critical roles in all stages atherosclerosis. Studies have confirmed that both ferroptosis promote atherosclerosis, but whether high level uric acid (HUA) promotes by regulating remains unclear. We found HUA significantly promoted atherosclerotic plaque downregulated protein NRF2/SLC7A11/GPX4 signaling pathway ApoE-/- mice. Next, we evaluated effect inhibitor ferrostatin-1 (Fer-1) treatment on formation macrophage-derived foam cells. cells, decreased cell viability, increased iron accumulation lipid peroxidation treated with oxidized low-density lipoprotein (oxLDL); these effects were reversed Fer-1 treatment. Mechanistically, inhibited autophagy pathway. activated upregulated ferroptosis-associated proteins. Moreover, an NRF2 inducer (tertbutyl hydroquinone (TBHQ)) activator (rapamycin (RAPA)) could reverse inhibitory survival. Our results suggest HUA-induced involved plaques. More importantly, enhancing inhibiting activating may alleviate These findings might contribute to a deeper understanding role pathogenesis provide therapeutic target ASVD associated hyperuricemia.

Language: Английский

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Ferroptosis Is Involved in Sex-Specific Small Intestinal Toxicity in the Offspring of Adult Mice Exposed to Polystyrene Nanoplastics during Pregnancy

ACS Nano, Journal Year: 2023, Volume and Issue: 17(3), P. 2440 - 2449

Published: Feb. 2, 2023

Nanoplastics are common contaminants in the living environment. Thus far, no investigations have focused on small intestinal injury offspring of adult mice that were exposed to nanoplastics through respiratory system during pregnancy. Here, we evaluated potential subjected maternal 80 nm polystyrene nanoparticle (PS-NP) exposure gestation. PS-NP significantly reduced birth weight female compared with male mice. However, body weights and substantially greater PS-NP-exposed groups. Additionally, found PS-NPs pregnancy caused histological changes intestines both offspring. Mechanistic analysis revealed upregulation reactive oxygen species intestines, as indicated by levels superoxide dismutase (SOD) malondialdehyde (MDA). Furthermore, led downregulation GPx4, FTH1, FTL protein levels, indicating initiation ferroptosis. Notably, mRNA expression differed between Although all phenotypes failed demonstrate classic dose-dependent effects, data imply toxicity is than Our results suggest causes sex-specific toxicity, which might contribute activation subsequent Overall, this study showed toxic effects after

Language: Английский

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