Edaravone Modulates Neuronal GPX4/ACSL4/5-LOX to Promote Recovery After Spinal Cord Injury

Pang, Yilin; Liu, Xinjie; Wang, Xu; Shi, Xuelian; Ma, Lei; Zhang, Yan; Zhou, Tiangang; Zhao, Chenxi; Zhang, Xu; Fan, Baoyou; Hao, Junhua; Li, Wenxiang; Zhao, Xiaoqing; Zhang, Rong; Zhou, Songlin; Kong, Xiaohong; Feng, Shiqing; Yao, Xuemei

doi:10.3389/fcell.2022.849854

Cited by 17 publications

(13 citation statements)

References 47 publications

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“…Edaravone is a free radical scavenger ( Dang et al, 2022 ). Pang et al (2022) found that edaravone upregulated GPX4/xCT and downregulated ACSL4/5-LOX to inhibit Ferroptosis during the acute phase of SCI in rats, thereby improving recovery of motor function in SCI.…”

Section: Related Substances That Improve Sci By Inhibiting Ferroptosismentioning

confidence: 97%

Ferroptosis is a new therapeutic target for spinal cord injury

Bai

Liu²,

Deng³

et al. 2023

Front. Neurosci.

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Spinal cord injury is a serious traumatic disease. As Ferroptosis has been increasingly studied in recent years, it has been found to be closely related to the pathophysiological processes of spinal cord injury. Iron overload, reactive oxygen species accumulation, lipid peroxidation and glutamate accumulation associated with Ferroptosis are all present in spinal cord injury, and thus Ferroptosis is thought to be involved in the pathological processes secondary to spinal cord injury. This article highlights the relationship between Ferroptosis and spinal cord injury, lists substances that improve spinal cord injury by inhibiting Ferroptosis, and concludes with a discussion of the problems that may be encountered in the clinical translation of Ferroptosis inhibitors as a means of enabling their faster use in clinical treatment.

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Section: Related Substances That Improve Sci By Inhibiting Ferroptosismentioning

confidence: 97%

Ferroptosis is a new therapeutic target for spinal cord injury

Bai

Liu²,

Deng³

et al. 2023

Front. Neurosci.

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“…Modulates prostaglandin E2 secretion. Preferred substrates: arachidonate (Klett et al, 2017) Central nervous system Glioma (Zhou et al, 2019;Cheng et al, 2020;Tan et al, 2020;Yee et al, 2020;Yi et al, 2020;Dattilo et al, 2021;Hacioglu and Kar, 2022;Kram et al, 2022;Miao et al, 2022) Cerebrovascular diseases: ischemic stroke (Gubern et al, 2013;Li et al, 2019;Chen J. et al, 2021;Cui et al, 2021;Guo H. et al, 2021;Li C. et al, 2021;Liao et al, 2021;Tuo et al, 2022), hemorrhage (Chen B. et al, 2021;Jin et al, 2021), subarachnoid hemorrhage (Qu et al, 2021;Huang et al, 2022;Yuan et al, 2022) Injury: traumatic brain injury (Kenny et al, 2019;Xiao et al, 2019;Bao Z. et al, 2021), spinal cord injury (Zhou et al, 2020;Pang et al, 2022) Intellectual disability: non-syndromic X-Linked intellectual developmental disorder (Meloni et al, 2009;Zhang et al, 2009;Liu et al, 2011Liu et al, , 2014Huang et al, 2016;Chang et al, 2019;Jia et al, 2019), Alport syndrome with intellectual disability (Rodriguez et al, 2010;Smetana et al, 2021) Neurodegenerative diseases: Alzheimer's disease (AD) (Rapoport, 2008;…”

Section: Gliomamentioning

confidence: 99%

“…For the past decade, ACSLs have drawn the researchers’ attention to the areas of brain tumor ( Yee et al, 2020 ), stroke ( Chang et al, 2019 ; Chen J. et al, 2021 ; Cui et al, 2021 ), injury ( Qu et al, 2021 ; Pang et al, 2022 ; Yuan et al, 2022 ), neurodegenerative disease ( Yao et al, 2021 ; Ben-Zaken et al, 2022 ) etc. ( Table 1 ).…”

Section: Introductionmentioning

confidence: 99%

“…Edaravone, a lipid peroxidation scavenger, has been approved by Food and Drug Administration as a neuroprotective effect on spinal cord injury (SCI) and many other central nervous system diseases. It can downregulate pro-ferroptosis proteins ACSL4 and 5-lipoxygenase (5-LOX), and reduce microgliosis and astrogliosis to promote recovery after SCI ( Pang et al, 2022 ). Proanthocyanidins (PACs) treatment has also been shown to mediate ferroptosis by significantly decreasing the levels of ACSL4 and iron in traumatic spinal cords and improving the locomotive function of SCI mice ( Zhou et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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An update on the therapeutic implications of long-chain acyl-coenzyme A synthetases in nervous system diseases

Sun

et al. 2022

Front. Neurosci.

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Long-chain acyl-coenzyme A synthetases (ACSLs) are a family of CoA synthetases that activate fatty acid (FA) with chain lengths of 12–20 carbon atoms by forming the acyl-AMP derivative in an isozyme-specific manner. This family mainly includes five members (ACSL1, ACSL3, ACSL4, ACSL5, and ACSL6), which are thought to have specific and different functions in FA metabolism and oxidative stress of mammals. Accumulating evidence shows that the dysfunction of ACSLs is likely to affect cell proliferation and lead to metabolic diseases in multiple organs and systems through different signaling pathways and molecular mechanisms. Hence, a central theme of this review is to emphasize the therapeutic implications of ACSLs in nervous system disorders.

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“…Given the critical role of ROS in SCI, edaravone is also nding its new application scope in ied of SCI. Multiple pre-clinical studies have shared a satisfactory e cacy of edaravone in treating this disease [17][18][19][20][21][22][23][24][25]. However, the integrated pre-clinical evidences focused on the neuroprotective effect of edaravone on SCI is still scarce.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective effect and possible mechanism of edaravone in rat models of spinal cord injury: a protocol for a systematic review and meta-analysis

Wang

Zhou

Chen

et al. 2023

Preprint

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Background: Spinal cord injury (SCI) is one of the most disabling and devastating neurological conditions, afflicting individuals and societies widely. Edaravone, a well-known synthetic ROS scavenger, is approved in the treatment of amyotrophic lateral sclerosis. In recent years, the role of edaravone in the treatment of SCI has been investigated in a growing number of studies. Methods: The systematic review will include the controlled studies evaluating the neurological roles of edaravone on experiment rat models following SCI. The primary outcome is the 21-point Basso, Beattie, and Bresnahan locomotor rating scale, and preservation of white matter areas and malondialdehyde will be employed as the secondary outcomes. Two researchers will search PubMed, Embase, Web of Science, Scopus and Cochrane Library from their inception date independently. Following study selection, data extraction, and assessment of methodological quality in the included studies using the SYRCLE’s RoB tool, data from eligible studies will be pooled and analyzed using random‑effects models with RevMan 5.3 software. In case of sufficient data, subgroup analyses with respect to species, age, sex, duration of intervention, dose or route of administration will be carried out to explore the factors modifying on BBB scores. For exploring the appropriate dose of edaravone, a network meta-analysis approach will be conducted based on the Bayesian method. Importantly, the proposed mechanisms and changes of related molecules will be also extracted from included studies for comprehensively investigating the neuroprotective mechanism behind edaravone. Discussion: In this study, we will quantitatively analyze the role of edaravone in locomotor recovery and tissue damage in SCI rat model. Besides, the efficacy of edaravone in distinct scenarios will be investigated by subgroups, and we plan to predict the candidate dose that exerts the greater neuroprotective effect with network meta-analyses. Moreover, we will provide comprehensive overview on the mechanisms underlying the emerging neuroprotective effects of edaravone in SCI. This study will provide implications for future preclinical studies and clinical applications of SCI.

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Edaravone Modulates Neuronal GPX4/ACSL4/5-LOX to Promote Recovery After Spinal Cord Injury

Cited by 17 publications

References 47 publications

Ferroptosis is a new therapeutic target for spinal cord injury

Ferroptosis is a new therapeutic target for spinal cord injury

An update on the therapeutic implications of long-chain acyl-coenzyme A synthetases in nervous system diseases

Neuroprotective effect and possible mechanism of edaravone in rat models of spinal cord injury: a protocol for a systematic review and meta-analysis

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