ArticleCells2020
Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) Enhances Activation of STAT3/NLRC4 Inflammasome Signaling Axis through PKCδ in Astrocytes: Implications for Parkinson's Disease.
Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Protein Kinase C-delta (PKCδ) in Neurodegeneration and Cerebral Ischemia: Molecular Mechanisms and Therapeutic Implications.Cell biochemistry and biophysics · 2026Review
- Exploring a specialized lactylation pattern to predict the prognosis and sensitivity of immunotherapy in breast cancer via machine learning.Breast cancer (Tokyo, Japan) · 2026Article
- Pathological α-synuclein dysregulates epitranscriptomic writer METTL3 to drive neuroinflammation in microglia.Cell reports · 2025Article
- Blood Progenitor Cell Mobilization Driven by TWEAK Promotes Neovascularization and Reduces Brain Damage in a Rat Model of Intracerebral Hemorrhage.Antioxidants (Basel, Switzerland) · 2025Article
- Exploring the hub Genes and Potential Mechanisms of Complement system-related Genes in Parkinson Disease: Based on Transcriptome Sequencing and Mendelian Randomization.Journal of molecular neuroscience : MN · 2024Article
- Protein Kinase C-Delta Mediates Cell Cycle Reentry and Apoptosis Induced by Amyloid-Beta Peptide in Post-Mitotic Cortical Neurons.International journal of molecular sciences · 2024Article
- Mitochondrial dysfunction in chronic neuroinflammatory diseases (Review).International journal of molecular medicine · 2024Review
- Role of inflammatory cytokine in mediating the effect of plasma lipidome on epilepsy: a mediation Mendelian randomization study.Frontiers in neurology · 2024Article
- Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson's disease.NPJ Parkinson's disease · 2023Article
- AKAP12 promotes cancer stem cell-like phenotypes and activates STAT3 in colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- The regulation roles of miRNAs in Helicobacter pylori infection.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Downregulation of SLC9A8 Promotes Epithelial-Mesenchymal Transition and Metastasis in Colorectal Cancer Cells via the IL6-JAK1/STAT3 Signaling Pathway.Digestive diseases and sciences · 2023Article
- Systems level analysis of sex-dependent gene expression changes in Parkinson's disease.NPJ Parkinson's disease · 2023Article
- TWEAK-Fn14 Axis Induces Calcium-Associated Autophagy and Cell Death To Control Mycobacterial Survival in Macrophages.Microbiology spectrum · 2022Article
- Aprepitant attenuates NLRC4-dependent neuronal pyroptosis via NK1R/PKCδ pathway in a mouse model of intracerebral hemorrhage.Journal of neuroinflammation · 2022Article
- TNF-like weak inducer of apoptosis / nuclear factor κB axis feedback loop promotes spinal cord injury by inducing astrocyte activation.Bioengineered · 2022Article
- Glial Cells and Brain Diseases: Inflammasomes as Relevant Pathological Entities.Frontiers in cellular neuroscience · 2022Review
- Crosstalk between neuroinflammation and oxidative stress in epilepsy.Frontiers in cell and developmental biology · 2022Review
- PKC Delta Activation Promotes Endoplasmic Reticulum Stress (ERS) and NLR Family Pyrin Domain-Containing 3 (NLRP3) Inflammasome Activation Subsequent to Asynuclein-Induced Microglial Activation: Involvement of Thioredoxin-Interacting Protein (TXNIP)/Thioredoxin (Trx) Redoxisome Pathway.Frontiers in aging neuroscience · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Astrocytic dysfunction has been implicated in Parkinson's disease (PD) pathogenesis. While the Tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 signaling axis is known to play a role in PD-like neuropathology, the molecular mechanisms that govern this process remain poorly understood. Herein, we show that TWEAK levels are elevated in PD serum compared to controls. Moreover, using both U373 human astrocyte cells and primary mouse astrocytes, we demonstrate that TWEAK induces mitochondrial oxidative stress as well as protein kinase C delta (PKCδ) and signal transducer and activator of transcription 3 (STAT3) activation, accompanied by NLRC4 inflammasome activation and upregulation and release of proinflammatory cytokines, including IL-1β, TNF-α, and IL-18. Mechanistically, TWEAK-induced PKCδ activation enhances the STAT3/NLRC4 signaling pathway and other proinflammatory mediators through a mitochondrial oxidative stress-dependent mechanism. We further show that PKCδ knockdown and mito-apocynin, a mitochondrial antioxidant, suppress TWEAK-induced proinflammatory NLRC4/STAT3 signaling and cellular oxidative stress response. Notably, we validated our in vitro findings in an MPTP mouse model of PD and in mice receiving intrastriatal administration of TWEAK. These results indicate that TWEAK is a key regulator of astroglial reactivity and illustrate a novel mechanism by which mitochondrial oxidative stress may influence dopaminergic neuronal survival in PD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.