Selective ferroptosis vulnerability due to familial Alzheimer’s disease presenilin mutations

Greenough, Mark; Lane, Darius J.R.; Balez, Rachelle; Anastacio, Helena Targa Dias; Zeng, Zhiwen; Ganio, Katherine; McDevitt, Christopher A.; Acevedo, Karla; Belaidi, Abdel Ali; Koistinaho, Jari; Ooi, Lezanne; Ayton, Scott; Bush, Ashley I.

doi:10.1038/s41418-022-01003-1

Cited by 43 publications

(28 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ferroptosis also plays a critical role in non-neoplastic diseases including neurogenic disease (e.g. Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease) ( 6–8 ), infectious diseases ( 9 ), autoimmune diseases ( 10 ), retinal diseases ( 11 ), tissue injuries ( 12 ) and some rare disorders ( 1 ). Collectively, ferroptosis is vitally implicated in a wide variety of diseases, as well as indicative for novel approaches of disease diagnosis, treatment, and prognosis prediction.…”

Section: Introductionmentioning

confidence: 99%

FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations

Zhou

Yuan

et al. 2022

Nucleic Acids Research

138

View full text Add to dashboard Cite

Ferroptosis is a mode of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation. It is closely linked to the pathophysiological processes in many diseases. Since our publication of the first ferroptosis database in 2020 (FerrDb V1), many new findings have been published. To keep up with the rapid progress in ferroptosis research and to provide timely and high-quality data, here we present the successor, FerrDb V2. It contains 1001 ferroptosis regulators and 143 ferroptosis-disease associations manually curated from 3288 articles. Specifically, there are 621 gene regulators, of which 264 are drivers, 238 are suppressors, 9 are markers, and 110 are unclassified genes; and there are 380 substance regulators, with 201 inducers and 179 inhibitors. Compared to FerrDb V1, curated articles increase by >300%, ferroptosis regulators increase by 175%, and ferroptosis-disease associations increase by 50.5%. Circular RNA and pseudogene are novel regulators in FerrDb V2, and the percentage of non-coding RNA increases from 7.3% to 13.6%. External gene-related data were integrated, enabling thought-provoking and gene-oriented analysis in FerrDb V2. In conclusion, FerrDb V2 will help to acquire deeper insights into ferroptosis. FerrDb V2 is freely accessible at http://www.zhounan.org/ferrdb/.

show abstract

Section: Introductionmentioning

confidence: 99%

FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations

Zhou

Yuan

et al. 2022

Nucleic Acids Research

138

View full text Add to dashboard Cite

show abstract

“…The hub genes allow for faster and easier evaluation of disease prognosis and provide the possibility of targeted interventions in these genes, which can aid in the treatment of AD. Additionally, our study focused more on gene screening, as compared to previous studies which mainly interpreted the role of ferroptosis in the pathogenesis of AD through proteins or their related pathways ( Chen K. et al, 2021 ; Greenough et al, 2022 ; Ma et al, 2022 ). The genes we identified are involved earlier in the disease process than protein production and subsequent pathogenic mechanisms, allowing for earlier screening of AD progression.…”

Section: Discussionmentioning

confidence: 99%

Constructing a prognostic risk model for Alzheimer’s disease based on ferroptosis

Wang¹,

Zhai²,

Li³

et al. 2023

Front. Aging Neurosci.

View full text Add to dashboard Cite

IntroductionThe aim of this study is to establish a prognostic risk model based on ferroptosis to prognosticate the severity of Alzheimer’s disease (AD) through gene expression changes.MethodsThe GSE138260 dataset was initially downloaded from the Gene expression Omnibus database. The ssGSEA algorithm was used to evaluate the immune infiltration of 28 kinds of immune cells in 36 samples. The up-regulated immune cells were divided into Cluster 1 group and Cluster 2 group, and the differences were analyzed. The LASSO regression analysis was used to establish the optimal scoring model. Cell Counting Kit-8 and Real Time Quantitative PCR were used to verify the effect of different concentrations of Aβ1–42 on the expression profile of representative genes in vitro.ResultsBased on the differential expression analysis, there were 14 up-regulated genes and 18 down-regulated genes between the control group and Cluster 1 group. Cluster 1 and Cluster 2 groups were differentially analyzed, and 50 up-regulated genes and 101 down-regulated genes were obtained. Finally, nine common differential genes were selected to establish the optimal scoring model. In vitro, CCK-8 experiments showed that the survival rate of cells decreased significantly with the increase of Aβ1–42 concentration compared with the control group. Moreover, RT-qPCR showed that with the increase of Aβ1–42 concentration, the expression of POR decreased first and then increased; RUFY3 was firstly increased and then decreased.DiscussionThe establishment of this research model can help clinicians make decisions on the severity of AD, thus providing better guidance for the clinical treatment of Alzheimer’s disease.

show abstract

“…Presenilin mutations may promote neurodegeneration by promoting ferroptosis, which highlights a disease‐modifying concept for therapeutics. [ 219 ] Allelic variation of APOE gene confers the greatest genetic risk for sporadic AD (SAD). Recent study reported that apoE activates the PI3K/AKT pathway to inhibit ferritinophagy, thus inhibiting iron‐dependent LPO.…”

Section: Ferroptosis In Neurological Diseasesmentioning

confidence: 99%

Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes

Wang

et al. 2023

Advanced Science

View full text Add to dashboard Cite

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

show abstract

Selective ferroptosis vulnerability due to familial Alzheimer’s disease presenilin mutations

Cited by 43 publications

References 96 publications

FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations

FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations

Constructing a prognostic risk model for Alzheimer’s disease based on ferroptosis

Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes

Contact Info

Product

Resources

About