Treatment and prevention of pathological mitochondrial dysfunction in retinal degeneration and in photoreceptor injury DOI Creative Commons
Walter H. Moos, Douglas V. Faller,

Ioannis P. Glavas

et al.

Biochemical Pharmacology, Journal Year: 2022, Volume and Issue: 203, P. 115168 - 115168

Published: July 12, 2022

Pathological deterioration of mitochondrial function is increasingly linked with multiple degenerative illnesses as a mediator wide range neurologic and age-related chronic diseases, including those genetic origin. Several these diseases are rare, typically defined in the United States an illness affecting fewer than 200,000 people U.S. population, or about one 1600 individuals. Vision impairment due to dysfunction eye prominent feature evident numerous primary common pathophysiology many familiar ophthalmic disorders, macular degeneration, diabetic retinopathy, glaucoma retinopathy prematurity — collection syndromes, disorders significant unmet medical needs. Focusing on metabolic pathway mechanisms, possible roles cuproptosis ferroptosis retinal dysfunction, we shed light potential α-lipoyl-L-carnitine treating diseases. α-Lipoyl-L-carnitine bioavailable mitochondria-targeting lipoic acid prodrug that has shown protecting against degeneration photoreceptor cell loss indications.

Language: Английский

Ethyl carbamate triggers ferroptosis in liver through inhibiting GSH synthesis and suppressing Nrf2 activation DOI Creative Commons
Yang Xu, Yuting Li, Jiaxin Li

et al.

Redox Biology, Journal Year: 2022, Volume and Issue: 53, P. 102349 - 102349

Published: May 22, 2022

Humans are inevitably exposed to ethyl carbamate (EC) via consumption of fermented food and beverages. EC, known as an environmental toxin, can cause oxidative stress-mediated severe toxicity, but the underlying mechanisms remain unveiled. Ferroptosis is a newly identified ROS-mediated non-apoptotic cell death characterized by iron accumulation excessive lipid oxidation. In this study, we first found that EC triggered ferroptosis in liver cells detection decreased viability, GSH, GPX4 Ferritin levels, well increased MDA contents. inhibitor ferrostatin-1 (Fer-1) pretreatment rescued ferroptotic damage, indicating was critical for EC-caused death. Furthermore, GSH synthesis precursor N-acetylcysteine displayed significant anti-ferroptotic properties suggested depletion might be main under exposure. EC-triggered mainly depended on suppressed inhibition SLC7A11 GCLC expressions. Notably, blocked Nrf2 activation repression phosphorylation modification nuclear translocation, which further resulted occurrence. We also observed EC-induced dysfunction inflammation, accompanied with stress, downregulated signaling Balb/c mice, could effectively reversed Fer-1 tBHQ pretreatment. Together, our study indicated new mechanism attributed inactivation depletion.

Language: Английский

Citations

148
Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes DOI Creative Commons
Yumin Wang, Shuang Wu, Qiang Li

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(24)

Published: June 21, 2023

Emerging evidence suggests that ferroptosis, a unique regulated cell death modality is morphologically and mechanistically different from other forms of death, plays vital role in the pathophysiological process neurodegenerative diseases, strokes. Accumulating supports ferroptosis as critical factor diseases strokes, pharmacological inhibition therapeutic target for these diseases. In this review article, core mechanisms are overviewed roles strokes described. Finally, emerging findings treating through This demonstrates by bioactive small-molecule compounds (ferroptosis inhibitors) could be effective treatments highlights potential promising avenue used to prevent article will shed light on developing novel regimens slow down progression future.

Language: Английский

Citations

86
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
Pharmacological inhibition of ferroptosis as a therapeutic target for sepsis-associated organ damage DOI
Liang Huo, Chunfeng Liu,

Yujun Yuan

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 257, P. 115438 - 115438

Published: May 13, 2023

Language: Английский

Citations

54
The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation DOI Creative Commons
Mohammad Sobhan Karvandi, Farzam Sheikhzadeh Hesari, Amir Reza Aref

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: March 6, 2023

Neuronal loss is one of the striking causes various central nervous system (CNS) disorders, including major neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), and Amyotrophic lateral sclerosis (ALS). Although these diseases have different features clinical manifestations, they share some common mechanisms pathology. Progressive regional neurons in patients responsible for motor, memory, cognitive dysfunctions, leading to disabilities death. cell death linked pathways conditions. Protein misfolding aggregation, mitochondrial dysfunction, generation reactive oxygen species (ROS), activation innate immune response are most critical hallmarks diseases. Thus, endoplasmic reticulum (ER) stress, oxidative neuroinflammation pathological factors neuronal Even though exact not fully discovered, notable role mentioned well known. On this basis, researchers been prompted investigate neuroprotective effects targeting underlying determine a promising therapeutic approach treatment. This review provides an overview ER death, mainly discussing or molecules involved factors.

Language: Английский

Citations

47
Ferroptosis as a mechanism of non-ferrous metal toxicity DOI
Michael Aschner, Anatoly V. Skalny, Airton C. Martins

et al.

Archives of Toxicology, Journal Year: 2022, Volume and Issue: 96(9), P. 2391 - 2417

Published: June 21, 2022

Language: Английский

Citations

65
Hinokitiol functions as a ferroptosis inhibitor to confer neuroprotection DOI
Junmin Xi, Zhijun Zhang, Zuo Wang

et al.

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 190, P. 202 - 215

Published: Aug. 17, 2022

Language: Английский

Citations

43
The contribution of an imbalanced redox signalling to neurological and neurodegenerative conditions DOI Creative Commons
Joern R. Steinert, Haitham Amal

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 194, P. 71 - 83

Published: Nov. 24, 2022

Language: Английский

Citations

41
Neurotoxic effects of air pollution: an urgent public health concern DOI
Deborah A. Cory‐Slechta, Marissa Sobolewski

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(3), P. 129 - 130

Published: Jan. 6, 2023

Language: Английский

Citations

26
Ferroptosis induces detrimental effects in chronic EAE and its implications for progressive MS DOI Creative Commons
Priya Jhelum, Stéphanie Zandee,

Fari Ryan

et al.

Acta Neuropathologica Communications, Journal Year: 2023, Volume and Issue: 11(1)

Published: July 25, 2023

Abstract Ferroptosis is a form of lipid peroxidation-mediated cell death and damage triggered by excess iron insufficiency in the glutathione antioxidant pathway. Oxidative stress thought to play crucial role progressive forms multiple sclerosis (MS) which deposition occurs. In this study we assessed if ferroptosis plays chronic experimental autoimmune encephalomyelitis (CH-EAE), mouse model used MS. Changes were detected mRNA levels several genes CH-EAE but not relapsing–remitting EAE. At protein level, expression importers increased earlier stages (onset peak). While hemoxygenase-1, mobilizes from heme, likely phagocytosed material, macrophages at peak stages. Excess cells stored safely ferritin, increases with disease progression. Harmful, redox active released ferritin when shuttled autophagosomes ‘nuclear receptor coactivator 4’ (NCOA4). NCOA4 accompanied increase ferrous iron. These changes occur parallel reduction pathway (system xCT, peroxidase 4 glutathione), peroxidation. Mice treated inhibitor for 2 weeks starting paralysis, show significant improvements function pathology. Autopsy samples tissue sections secondary MS (SPMS) showed oligodendrocytes along rim mixed active/inactive lesions, where ferritin+ containing are located. Cells expressing express less suggesting degradation release iron, as indicated data suggest that contribute pathogenesis SPMS.

Language: Английский

Citations

23