Activation of p62-Keap1-Nrf2 Pathway Protects 6-Hydroxydopamine-Induced Ferroptosis in Dopaminergic Cells

Sun, Yiran; He, Libo; Wang, Taoyu; Wei, Hua; Qin, Huan; Wang, Jingjin; Wang, Li; Gu, Wanqin; Li, Tingting; Li, Na; Liu, Xinanbei; Chen, Fang; Tang, Lin

doi:10.1007/s12035-020-02049-3

Cited by 106 publications

(81 citation statements)

References 59 publications

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“…Once the basic knowledge such as molecular mechanism and regulation of ferroptosis is recognized, a spectrum of potential clinical applications, including drug discovery and development, will follow. For application studies, ferroptosis pathways have gained attention as novel therapeutic targets for treatment of many diseases, in particular for cancers and neurodegenerative diseases ( Chen et al, 2015 ; Liang et al, 2019 ; Lelièvre et al, 2020 ; Reichert et al, 2020 ; Sun et al, 2020 ). Therefore, parallel to the mechanism studies of ferroptosis, further studies should focus on clinical application and transformation research.…”

Section: Discussionmentioning

confidence: 99%

“…Over the past few years, the cumulative evidence indicated that impaired ferroptosis is implicated in the development of various pathological conditions, most notably cancer ( Zielke et al, 2018 ; Yang et al, 2019 , 2020 ), neurodegenerative diseases ( Reichert et al, 2020 ; Sun et al, 2020 ), tissue ischemia/reperfusion injury ( Tuo et al, 2017 ; Li et al, 2019 ), craniocerebral trauma ( Tang et al, 2020 ), and inflammation ( Proneth and Conrad, 2019 ). Therefore, it is a promising field to develop potent ferroptosis inducers or inhibitors with high potential for preventing and treating the aforementioned diseases, as well as several other underlying disorders related to ferroptosis.…”

Section: Introductionmentioning

confidence: 99%

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Global Research Trends of Ferroptosis: A Rapidly Evolving Field With Enormous Potential

Wang

Tong

et al. 2021

Front. Cell Dev. Biol.

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Background: Ferroptosis is a newly proposed form of programmed cell death, and accumulating evidence suggests that it plays an essential role in the development of multiple diseases, especially cancers and neurodegenerative diseases. Since officially named in 2012, research on ferroptosis has grown rapidly. There are previous reviews focused on the research progress of ferroptosis from a certain aspect, but no bibliometric studies summarizing this field as a whole. This study aimed to assess the scientific output and activity regarding ferroptosis research from a global perspective.Methods: Publications related to ferroptosis from 2012 to 2020 were identified and selected from the Web of Science Core Collection. Excel 2019 and GraphPad Prism 8.0 was used to analyze quantitative variables including number of publications and citations, H-index, and journal citation reports. VOS viewer and CiteSpace were used to perform co-authorship, co-citation, and co-occurrence analysis of countries/institutes/authors/keywords.Results: A total of 1,285 publications on ferroptosis research were identified. The literature on ferroptosis had been continuously growing since 2012, and the expansion might continue at a rapid pace in the following years. China contributed the greatest proportion (43.74%) of ferroptosis publications, and the United States ranked first in the number of citation frequency (20,980 times) and H-index (70). B. R. Stockwell, D. L. Tang, and R. Kang were key researchers. The journal Cell Death Disease published the highest number of articles, with 42 articles. All the keywords could be divided into two clusters: cluster 1 (pathway and mechanism) and cluster 2 (treatment and effect). In terms of potential hotspots, keywords with the strong bursts and still ongoing recently were “neurodegeneration” (2017–2020), “chemotherapy” (2017–2020), “NF-kappa B” (2017–2020), and “photodynamic therapy” (2018–2020).Conclusion: There will be a dramatically increasing number of publications on ferroptosis research based on the current global trends. China has made significant progress in ferroptosis research, but the United States is actually dominated in this field. More focus will be placed on neurodegeneration, chemotherapy, nuclear factor κB, and photodynamic therapy, which may be the next popular topics in ferroptosis research.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Global Research Trends of Ferroptosis: A Rapidly Evolving Field With Enormous Potential

Wang

Tong

et al. 2021

Front. Cell Dev. Biol.

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“…Previous researches have veri ed that Nrf2 mostly translocates to the nucleus in the dopaminergic neurons in the substantia nigra of PD patients, while it is present in the cytoplasm in the matched normal control group of the same age [16,24,25]. Besides, studies have also demonstrated that overexpression of Nrf2 can reduce the damage of 6-OHDA in dopaminergic neurons [19,26]. Under physiological condition, Nrf2 protein expression levels were low in cells, mainly in the cytoplasm, where it can interact with Kelch-like ECH associated protein-1 (Keap1) [27,28].…”

Section: Discussionmentioning

confidence: 98%

Chinese Medicine PaBing-II Protects Human iPSC Derived Dopaminergic Neurons from Oxygen Stress

Wu¹,

Lin²,

Xu³

2021

Preprint

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BackgroundPaBing-II Formula (PB-II) is a traditional Chinese medicine developed to treat Parkinson's disease (PD). However, due to the complexity of PB-II and the difficulty of culturing human dopaminergic neurons (DAn) in vitro, the mechanism of PB-II to treat PD remains unclear. MethodsWe established the human induced pluripotent stem cells (iPSCs) and derived DAn from hiPSCs to study the protective effects of PB-II on DAn after oxidative stress, which plays an important role in PD pathogenesis. ResultsWe found that serum derived from rats that had ingested PB-II significantly protect hiPSC-derived DAn from reactive oxygen species (ROS). In addition, PB-II dependent serum can activate nuclear erythroid-derived factor 2 (Nrf2) responses, which are required for the neutralization of ROS. In addition, PB-II can activate the Nrf2/ARE signal pathway of midbrain dopaminergic neurons of PD rats induced with 6-hydroxydopamine (6-OHDA) injury, rescue DAn cells, and improve the symptoms of PD rats. ConclusionsPB-II significantly protects the DA neurons from oxidative stress by activating the Nrf2 pathway.

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“…6-OHDA has been reported inducing ferroptosis in an in vitro model using SH-SY5Y cells (Sun et al, 2020). In contrast, there is a report demonstrating that the non-oxidative form of dopamine can inhibit erastin-induced ferroptosis (Wang et al, 2016).…”

Section: -Ohdamentioning

confidence: 99%

Chemically Induced Models of Parkinson’s Disease: History and Perspectives for the Involvement of Ferroptosis

Wen

Aki

Unuma

et al. 2020

Front. Cell. Neurosci.

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Ferroptosis is a newly discovered form of necrotic cell death characterized by its dependency on iron and lipid peroxidation. Ferroptosis has attracted much attention recently in the area of neurodegeneration since the involvement of ferroptosis in Parkinson’s disease (PD), a major neurodegenerative disease, has been indicated using animal models. Although PD is associated with both genetic and environmental factors, sporadic forms of PD account for more than 90% of total PD. Following the importance of environmental factors, various neurotoxins are used as chemical inducers of PD both in vivo and in vitro. In contrast to other neurodegenerative diseases such as Alzheimer’s and Huntington’s diseases (AD and HD), many of the characteristics of PD can be reproduced in vivo by the use of specific neurotoxins. Given the indication of ferroptosis in PD pathology, several studies have been conducted to examine whether ferroptosis plays role in the loss of dopaminergic neurons in PD. However, there are still few reports showing an authentic form of ferroptosis in neuronal cells during exposure to the neurotoxins used as PD inducers. In this review article, we summarize the history of the uses of chemicals to create PD models in vivo and in vitro. Besides, we also survey recent reports examining the possible involvement of ferroptosis in chemical models of PD.

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Activation of p62-Keap1-Nrf2 Pathway Protects 6-Hydroxydopamine-Induced Ferroptosis in Dopaminergic Cells

Cited by 106 publications

References 59 publications

Global Research Trends of Ferroptosis: A Rapidly Evolving Field With Enormous Potential

Global Research Trends of Ferroptosis: A Rapidly Evolving Field With Enormous Potential

Chinese Medicine PaBing-II Protects Human iPSC Derived Dopaminergic Neurons from Oxygen Stress

Chemically Induced Models of Parkinson’s Disease: History and Perspectives for the Involvement of Ferroptosis

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