The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Language: Английский

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Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Language: Английский

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Pathology of pain and its implications for therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 8, 2024

Abstract Pain is estimated to affect more than 20% of the global population, imposing incalculable health and economic burdens. Effective pain management crucial for individuals suffering from pain. However, current methods assessment treatment fall short clinical needs. Benefiting advances in neuroscience biotechnology, neuronal circuits molecular mechanisms critically involved modulation have been elucidated. These research achievements incited progress identifying new diagnostic therapeutic targets. In this review, we first introduce fundamental knowledge about pain, setting stage subsequent contents. The review next delves into underlying disorders, including gene mutation, epigenetic modification, posttranslational inflammasome, signaling pathways microbiota. To better present a comprehensive view research, two prominent issues, sexual dimorphism comorbidities, are discussed detail based on findings. status quo evaluation manipulation summarized. A series improved innovative strategies, such as therapy, monoclonal antibody, brain-computer interface microbial intervention, making strides towards application. We highlight existing limitations future directions enhancing quality preclinical research. Efforts decipher complexities pathology will be instrumental translating scientific discoveries practice, thereby improving bench bedside.

Language: Английский

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Harnessing luciferase chemistry in regulated cell death modalities and autophagy: overview and perspectives

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

This review provides a comprehensive overview of the use bioluminescence assays in advancing our understanding and studying cell death modalities autophagy.

Language: Английский

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Mitochondria-targeting peptide SS-31 attenuates ferroptosis via inhibition of the p38 MAPK signaling pathway in the hippocampus of epileptic rats

Brain Research, Journal Year: 2024, Volume and Issue: 1836, P. 148882 - 148882

Published: March 21, 2024

Language: Английский

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Suppression of Skp2 contributes to sepsis-induced acute lung injury by enhancing ferroptosis through the ubiquitination of SLC3A2

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: July 30, 2024

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. The inflammatory cytokine storm causes systemic damage, especially acute lung injury in sepsis. In this study, we found that the expression of S-phase kinase-associated protein 2 (Skp2) was significantly decreased sepsis-induced (ALI). activated MEK/ERK pathway and inhibited Skp2 pulmonary epithelium, resulting reduction K48 ubiquitination solute carrier family 3 member (SLC3A2), thereby impairing its membrane localization cystine/glutamate exchange function. Consequently, intracellular redox reactions induced ferroptosis epithelial cells, leading injury. Finally, demonstrated intravenous administration mRNA-encapsulating lipid nanoparticles (LNPs) epithelium alleviated septic mice. Taken together, these data provide an innovative understanding underlying mechanisms ALI promising therapeutic strategy for

Language: Английский

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Mechanisms of Cancer-Induced Bone Pain

Journal of Pain Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 315 - 326

Published: Jan. 1, 2025

Bone is a common site of advanced cancer metastasis, second only to the lungs and liver.Cancer-induced bone pain (CIBP) persistent intense that caused by combination inflammatory neuropathic factors.As CIBP progresses, degree intensifies.Despite advancements in medical technology, treatment outcomes patients with remain unsatisfactory, severe can typically be controlled opioid medications.However, treated medications often develop tolerance.Therefore, they may require dose increases, which increase severity opioid-induced side effects, turn influencing quality life.The peripheral mechanisms primarily involve tissue damage, tumor microenvironment formation, changes dorsal root ganglion.The central usually biochemical electrophysiological spinal cord brain.The main processing center for nociceptive signals.When cells produce mediators acidify or damage nerve endings, becomes excessively stimulated, resulting increased prolonged signals propagate higher nervous system through ascending pathway.There are substantial differences generation between pain.Therefore, understanding underpinning development at level crucial optimizing management.This study explores pathogenesis describes recently proposed methods CIBP.

Language: Английский

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Sodium Danshensu Alleviates Bone Cancer Pain by Inhibiting the Osteoclast Differentiation and CGRP Expression

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: 992, P. 177296 - 177296

Published: Feb. 1, 2025

Language: Английский

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Per2 deficiency in microglia alleviates motor dysfunction by inhibiting ferroptosis in spinal cord injury

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Microglia are specialized resident immune cells of the central nervous system parenchyma that mediate reactions such as inflammatory response to spinal cord injury (SCI) and play significant roles in exacerbating or alleviating disease progression. Previous studies have suggested ferroptosis, a newly discovered form regulated necrotic cell death, plays crucial role neuronal dysfunction loss following SCI; however, microglial ferroptosis SCI underlying mechanisms remain elusive. Here, we elucidate lipid droplets accumulate microglia facilitate after SCI. Notably, peaks at 3 days post-injury, which it decreases. Microglial Period 2 (Per2) expression is elevated vivo, this change highly synchronized with changes ferroptosis. Using conditional knockout mice, observed microglia-specific Per2 promoted neurological function recovery by suppressing In vitro, overexpression deficiency amplified mitigated respectively. RNA-seq analysis, found Gpx4 was downregulated Per2. Coimmunoprecipitation (Co-IP) demonstrated directly interacted PPARα further regulate Gpx4. Furthermore, degree decreased number increased treatment inhibitor, indicated reducing during acute phase may be beneficial for dysfunction. Overall, our results indicate determines susceptibility via PPARα-Gpx4 axis, suggest has potential therapeutic strategy alleviate motor inhibiting

Language: Английский

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Effect of Engineered Cyanobacterial Capsules on a Neurogenic Bladder after Spinal Cord Injury

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

The presence of a neurogenic bladder is severe but common complication spinal cord injury (SCI). Multiple pathological factors, such as hypoxia, ischemia, and oxidative stress caused by SCI, promote M1 microglial polarization the release proinflammatory factors to amplify inflammation. An excessive inflammatory response stimulates generation reactive oxygen species (ROS) induces neuronal ferroptosis, thus leading dysfunction after SCI. Therefore, promoting recovery neural function regulating interaction between microglia neurons important. For this purpose, we developed an engineered immunoregulatory cyanobacterial capsule named siRNA@Cyanzyme, which consists MnO2@zeolitic-imidazolate framework@cyanobacteria (Cyanzyme) small-interfering RNA targeting ACSL4 (siRNA-ACSL4). Cyanzyme reversed via photosynthetic anti-inflammatory factor release. MnO2 nanoenzymes grown on surface ZIF-8 eliminated ROS reduce stress. Moreover, increased delivery efficiency siRNA-ACSL4, key regulator ferroptosis. Both treatments alleviated GABAergic neuron damage mitigate dysfunction. Our data demonstrated that siRNA@Cyanzyme effectively polarization, reduced ultimately restored function.

Language: Английский

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