The multifaceted roles of activating transcription factor 3 (ATF3) in inflammatory responses – Potential target to regulate neuroinflammation in acute brain injury

Li, Yan; Fan, Qiuyue; Li, Fengshi; Pang, Rui; Chen, Chen; Li, Peiying; Wang, Xin; Xuan, Wei; Yu, Weifeng

doi:10.1177/0271678x231171999

Cited by 3 publications

(2 citation statements)

References 117 publications

(214 reference statements)

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“…A nuclear calcium-CREB signaling to an ATF3-mediated neuroprotective gene repression program counteracts age- and disease-related neuronal loss [ 64 ]. Nonetheless, ATF3 modulates inflammatory responses during injury, leading to cell death [ 65 , 66 , 67 ].…”

Section: Wwox Exhibits Multiple Functional Propertiesmentioning

confidence: 99%

Zfra Overrides WWOX in Suppressing the Progression of Neurodegeneration

Chen,

Liu,

Wen

et al. 2024

IJMS

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We reported that a 31-amino-acid Zfra protein (zinc finger-like protein that regulates apoptosis) blocks neurodegeneration and cancer growth. Zfra binds WW domain-containing oxidoreductase (WWOX) to both N- and C-termini, which leads to accelerated WWOX degradation. WWOX limits the progression of neurodegeneration such as Alzheimer’s disease (AD) by binding tau and tau-hyperphosphorylating enzymes. Similarly, Zfra binds many protein targets and accelerates their degradation independently of ubiquitination. Furthermore, Zfra4-10 peptide strongly prevents the progression of AD-like symptoms in triple-transgenic (3xTg) mice during aging. Zfra4-10 peptide restores memory loss in 9-month-old 3xTg mice by blocking the aggregation of a protein cascade, including TPC6AΔ, TIAF1, and SH3GLB2, by causing aggregation of tau and amyloid β. Zfra4-10 also suppresses inflammatory NF-κB activation. Zfra-activated Hyal-2+ CD3- CD19- Z cells in the spleen, via Hyal-2/WWOX/Smad4 signaling, are potent in cancer suppression. In this perspective review, we provide mechanistic insights regarding how Zfra overrides WWOX to induce cancer suppression and retard AD progression via Z cells.

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Section: Wwox Exhibits Multiple Functional Propertiesmentioning

confidence: 99%

Zfra Overrides WWOX in Suppressing the Progression of Neurodegeneration

Chen,

Liu,

Wen

et al. 2024

IJMS

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“…Thus, future research must investigate the exact regulatory functions of Atf3 in both acute and late stages of brain injury to establish the potential role of Atf3 as a biomarker or therapeutic target. 10…”

mentioning

confidence: 99%

Recent advances in mechanistic, therapeutic, and diagnostic research of cerebrovascular diseases: updates from brain & BrainPET 2022

Guo,

Li,

Boltze

2023

J Cereb Blood Flow Metab

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Cerebrovascular dysfunction and diseases are major causes of mortality, morbidity, and poor quality of patient life. Despite the enormous socioeconomic burden imposed by these conditions, therapeutic options remain scarce. However, rigorous preclinical and clinical research has augmented our mechanistic understanding of cerebrovascular diseases and underlying pathophysiological processes, and there is some optimism that novel therapeutic strategies may be developed in the next decade. This special collection comprises preclinical and clinical studies from investigators who presented their work at the Brain & BrainPET 2022 conference. It highlights recent research on cerebrovascular disease mechanisms, diagnosis, and treatments. A focus is set on cerebroprotective strategies during acute and chronic cerebral ischemia and predicting stroke risk and unfavorable outcomes. The special collection also sheds light on emerging novel treatment targets and management strategies in the pursuit of better clinical outcomes for patients with cerebrovascular diseases.

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Bioinformatics and next generation data analysis reveals the potential role of inflammation in sepsis and its associated complications

Vastrad¹,

Vastrad²

2023

Preprint

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Sepsis is the leading systemic inflammatory response syndrome in worldwide, yet relatively little is known about the genes and signaling pathways involved in sepsis progression. The current investigation aimed to elucidate potential key candidate genes and pathways in sepsis and its associated complications. Next generation sequencing (NGS) dataset (GSE185263) was downloaded from the Gene Expression Omnibus (GEO) database, which included data from 348 sepsis samples and 44 normal control samples. Differentially expressed genes (DEGs) were identified using t-tests in the DESeq2 R package. Next, we made use of the g:Profiler to analyze gene ontology (GO) and REACTOME pathway. Then protein-protein interaction (PPI) of these DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). Furthermore, we constructed miRNA-hub gene regulatory network and TF-hub gene regulatory network among hub genes utilizing miRNet and NetworkAnalyst online databases tool and Cytoscape software. Finally, we performed receiver operating characteristic (ROC) curve analysis of hub genes through the pROC package in R statistical software. In total, 958 DEGs were identified, of which 479 were up regulated and 479 were down regulated. GO and REACTOME results showed that DEGs mainly enriched in regulation of cellular process, response to stimulus, extracellular matrix organization and immune system. The hub genes of PRKN, KIT, FGFR2, GATA3, ERBB3, CDK1, PPARG, H2BC5, H4C4 and CDC20 might be associated with sepsis and its associated complications. Predicted miRNAs (e.g., hsa-mir-548ad-5p and hsa-mir-2113) and TFs (e.g., YAP1 and TBX5) were found to be significantly correlated with sepsis and its associated complications. In conclusion, the DEGs, relative pathways, hub genes, miRNA and TFs identified in the current investigation might help in understanding of the molecular mechanisms underlying sepsis and its associated complications progression and provide potential molecular targets and biomarkers for sepsis and its associated complications.

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The multifaceted roles of activating transcription factor 3 (ATF3) in inflammatory responses – Potential target to regulate neuroinflammation in acute brain injury

Cited by 3 publications

References 117 publications

Zfra Overrides WWOX in Suppressing the Progression of Neurodegeneration

Zfra Overrides WWOX in Suppressing the Progression of Neurodegeneration

Recent advances in mechanistic, therapeutic, and diagnostic research of cerebrovascular diseases: updates from brain & BrainPET 2022

Bioinformatics and next generation data analysis reveals the potential role of inflammation in sepsis and its associated complications

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