Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer’s disease DOI Creative Commons
Yanxin Shen, Guimei Zhang,

Chunxiao Wei

et al.

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(3), P. 613 - 631

Published: March 1, 2024

Alzheimer’s disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, cure for has not yet been found. Oxidative stress mediates excessive oxidative responses, its involvement in pathogenesis as primary or secondary pathological event widely accepted. As member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With discovery ferroptosis, central role anti-lipid peroxidation several diseases, including disease, received widespread attention. Increasing evidence suggests that expression inhibited brain, resulting stress, inflammation, apoptosis, which are closely associated damage disease. Several therapeutic approaches, such small molecule drugs, natural plant products, non-pharmacological treatments, ameliorate cognitive function by promoting enhancing activity. Therefore, upregulation may be promising strategy treatment This review provides overview gene structure, biological functions, regulatory mechanisms 4, discussion on important events related summary advances small-molecule therapies targeting Most prior studies this subject used animal models, relevant clinical lacking. Future trials required validate effects strategies

Language: Английский

Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism DOI Creative Commons
Zhifu Cui, Xingtao Zhao, Felix Kwame Amevor

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 22, 2022

Quercetin, a naturally non-toxic flavonoid within the safe dose range with antioxidant, anti-apoptotic and anti-inflammatory properties, plays an important role in treatment of aging-related diseases. Sirtuin 1 (SIRT1), member NAD+-dependent deacetylase enzyme family, is extensively explored as potential therapeutic target for attenuating aging-induced disorders. SIRT1 possess beneficial effects against diseases such Alzheimer's disease (AD), Parkinson's (PD), Huntington's (HD), Depression, Osteoporosis, Myocardial ischemia (M/I) reperfusion (MI/R), Atherosclerosis (AS), Diabetes. Previous studies have reported that aging increases tissue susceptibility, whereas, regulates cellular senescence multiple processes, including SIRT1/Keap1/Nrf2/HO-1 SIRTI/PI3K/Akt/GSK-3β mediated oxidative stress, SIRT1/NF-κB SIRT1/NLRP3 regulated inflammatory response, SIRT1/PGC1α/eIF2α/ATF4/CHOP SIRT1/PKD1/CREB controlled phosphorylation, SIRT1-PINK1-Parkin mitochondrial damage, SIRT1/FoxO autophagy, SIRT1/FoxG1/CREB/BDNF/Trkβ-catenin neuroprotective effects. In this review, we summarized improvement attenuation effect quercetin on relationship between relevant signaling pathways by SIRT1. Moreover, functional regulation markers function, autophagy apoptosis through was discussed. Finally, prospects extracellular vesicles (EVs) loading delivery, SIRT1-mediated EVs signal carriers treating diseases, well discussed ferroptosis alleviation to protect via activating Generally, may serve promising inhibiting reducing responses, restoring dysfunction.

Language: Английский

Citations

210
Iron Dyshomeostasis and Ferroptosis: A New Alzheimer’s Disease Hypothesis? DOI Creative Commons
Feixue Wang, Jiandong Wang, Ying Shen

et al.

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: March 22, 2022

Iron plays a crucial role in many physiological processes of the human body, but iron is continuously deposited brain as we age. Early studies found overload directly proportional to cognitive decline Alzheimer’s disease (AD). Amyloid precursor protein (APP) and tau protein, both which are related AD pathogenesis, associated with metabolism. A variety metabolism-related proteins have been be abnormally expressed brains patients mouse models, resulting deposition promoting progression. β (Aβ) hyperphosphorylated tau, two pathological hallmarks AD, can also promote brain, forming vicious cycle development-iron deposition. subsequent ferroptosis has potential mechanism underlying neuronal loss neurodegenerative diseases. chelators, antioxidants hepcidin were useful for treating represents an important direction treatment research drug development future. The review explored deep connection between dysregulation discussed new hypothesis dyshomeostasis ferroptosis, summarized therapeutics capable targeting iron, expectation draw more attention corresponding development.

Language: Английский

Citations

108
Ferroptosis: regulation by competition between NRF2 and BACH1 and propagation of the death signal DOI Open Access
Hironari Nishizawa, Mie Yamanaka, Kazuhiko Igarashi

et al.

FEBS Journal, Journal Year: 2022, Volume and Issue: 290(7), P. 1688 - 1704

Published: Feb. 2, 2022

Ferroptosis is triggered by a chain of intracellular labile iron-dependent peroxidation cell membrane phospholipids. important not only as cause ischaemic and neurodegenerative diseases but also mechanism cancer suppression, better understanding its regulatory required. It has become clear that ferroptosis finely controlled two oxidative stress-responsive transcription factors, NRF2 (NF-E2-related factor 2) BACH1 (BTB CNC homology 1). inhibit promote ferroptosis, respectively, activating or suppressing the expression genes in major pathways ferroptosis: iron metabolism, GSH (glutathione) -GPX4 (glutathione peroxidase 4) pathway FSP1 (ferroptosis suppressor protein 1)-CoQ (coenzyme Q) pathway. In addition to this, control through regulation lipid metabolism differentiation. This multifaceted considered have been acquired during evolution multicellular organisms, allowing utilization for maintaining homeostasis, including suppression. terms cell-cell interaction, it revealed property propagating surrounding cells along with peroxidation. The propagation phenomenon could be used realize anticancer therapy future. this review, these points will summarized discussed.

Language: Английский

Citations

98
Cerebral Iron Deposition in Neurodegeneration DOI Creative Commons
Petr Dušek, Tim Hofer, Jan Alexander

et al.

Biomolecules, Journal Year: 2022, Volume and Issue: 12(5), P. 714 - 714

Published: May 17, 2022

Disruption of cerebral iron regulation appears to have a role in aging and the pathogenesis various neurodegenerative disorders. Possible unfavorable impacts accumulation include reactive oxygen species generation, induction ferroptosis, acceleration inflammatory changes. Whole-brain iron-sensitive magnetic resonance imaging (MRI) techniques allow examination macroscopic patterns brain deposits vivo, while modern analytical methods ex vivo enable determination metal-specific content inside individual cell-types, sometimes also within specific cellular compartments. The present review summarizes whole brain, cellular, subcellular diseases genetic sporadic origin. We provide an update on mechanisms, biomarkers, effects these disorders, focusing recent publications. In Parkinson’s disease, Friedreich’s several disorders neurodegeneration with group, there is focal siderosis, typically regions most pronounced neuropathological second group including multiple sclerosis, Alzheimer’s amyotrophic lateral sclerosis shows globus pallidus, caudate, putamen, cortical regions. Yet, other such as aceruloplasminemia, neuroferritinopathy, or Wilson disease manifest diffuse deep gray matter pattern comparable even more extensive than that observed during normal aging. On microscopic level, are mostly dystrophic microglia variably accompanied by iron-laden macrophages astrocytes, implicating changes blood–brain barrier disturbance accumulation. Options potential benefits reducing strategies discussed. Future research investigating whether predispositions play Fe necessary. If confirmed, prevention further uptake individuals at risk may be key for preventing

Language: Английский

Citations

92
Targeting Molecular Mediators of Ferroptosis and Oxidative Stress for Neurological Disorders DOI Creative Commons
Jing Li,

Bowen Jia,

Ying Cheng

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 14

Published: July 22, 2022

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

Language: Английский

Citations

80
Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases DOI Creative Commons
Yumin Wang, Jing Hu, Shuang Wu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

Citations

77
Salidroside alleviates cognitive impairment by inhibiting ferroptosis via activation of the Nrf2/GPX4 axis in SAMP8 mice DOI Creative Commons
Sixia Yang, Linshuang Wang, Yi Zeng

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 114, P. 154762 - 154762

Published: March 14, 2023

Alzheimer's disease (AD) is a neurogenerative and remains no effective method for stopping its progress. Ferroptosis adaptive immunity have been proven to contribute AD pathogenesis. Salidroside exhibits neuroprotective immunomodulatory effects. However, the underlying mechanisms linking salidroside, ferroptosis, in remain uncertain.The objective of this study explore effects potential molecular salidroside against neuronal ferroptosis CD8+ T cell infiltration senescence-accelerated mouse prone 8 (SAMP8) mice.SAMP8 mice were employed as an model treated with 12 weeks. Behavioral tests, immunohistochemistry, HE Nissl staining, immunofluorescence, transmission electron microscopy, quantitative proteomics, bioinformatic analysis, flow cytometry, iron western blotting, docking performed.Treatment dose-dependently attenuated cognitive impairment, reduced accumulation Aβ plaques restored damage. also suppressed CD8+T cells, oxidative stress, inflammatory cytokines, improved mitochondrial metabolism, lipid redox SAMP8 brain. The administration decreased deposition, TFR1, ACSL4 protein expression, upregulated SLC7A11, GPX4 promoted Nrf2/GPX4 axis activation.In conclusion, cells are involved process impairment mice. alleviates inhibits ferroptosis. may involve activation reduction infiltration. This provides some evidence roles

Language: Английский

Citations

69
GPX4, ferroptosis, and diseases DOI Open Access

Wangzheqi Zhang,

Yang Liu,

Liao Yan

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116512 - 116512

Published: April 3, 2024

GPX4 (Glutathione peroxidase 4) serves as a crucial intracellular regulatory factor, participating in various physiological processes and playing significant role maintaining the redox homeostasis within body. Ferroptosis, form of iron-dependent non-apoptotic cell death, has gained considerable attention recent years due to its involvement multiple pathological processes. is closely associated with ferroptosis functions primary inhibitor this process. Together, contribute pathophysiology several diseases, including sepsis, nervous system ischemia reperfusion injury, cardiovascular cancer. This review comprehensively explores roles impacts development progression these aim providing insights for identifying potential therapeutic strategies future.

Language: Английский

Citations

58
Iron imbalance in neurodegeneration DOI Creative Commons
Sonia Levi, Maddalena Ripamonti, Andrea Stefano Moro

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(4), P. 1139 - 1152

Published: Jan. 12, 2024

Iron is an essential element for the development and functionality of brain, anomalies in its distribution concentration brain tissue have been found to be associated with most frequent neurodegenerative diseases. When magnetic resonance techniques allowed iron quantification vivo, it was confirmed that alteration homeostasis a common feature many However, whether main actor process, or consequence degenerative process still open question. Because different iron-related pathogenic mechanisms are specific distinctive diseases, identifying molecular various pathologies could represent way clarify this complex topic. Indeed, both overload deficiency profound consequences on cellular functioning, contribute neuronal death processes manners, such as promoting oxidative damage, loss membrane integrity, proteostasis, mitochondrial dysfunction. In review, attempt elucidate dyshomeostasis health, we summarize pathological couple death.

Language: Английский

Citations

56
Berberine ameliorates iron levels and ferroptosis in the brain of 3 × Tg-AD mice DOI
Xinlu Li, Jianfeng Chen,

Wennuo Feng

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 118, P. 154962 - 154962

Published: July 17, 2023

Language: Английский

Citations

52