Targeting NINJ1-mediated cell rupture to treat inflammatory diseases DOI Creative Commons

Claire Ju-Eun Hur,

Benjamin E. Steinberg

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: Feb. 14, 2025

Abstract Cell death can terminate in plasma membrane rupture to release potent pro-inflammatory intracellular contents thereby contributing inflammatory diseases. is an active process, mediated by the protein ninjurin-1 (NINJ1) pyroptosis, post-apoptosis lysis, ferroptosis, and forms of necrosis. Once activated, NINJ1 clusters into large oligomers within initiate cellular lysis. Recent preclinical studies have demonstrated that inhibiting a new strategy for treating immune-mediated Indeed, both small molecule inhibitors neutralizing antibodies target clustering preserve integrity mitigate disease pathogenesis. In this Perspective , we provide summary current state knowledge recent developments targeting during cell through inhibition treat disease, with focus on liver injury. As these NINJ1-mediated pathways are pivotal maintaining health contribute pathogenesis when dysregulated, discussed broad implications across immunologic basis molecular medicine.

Language: Английский

Synthetic protein circuits for programmable control of mammalian cell death DOI Creative Commons
Shiyu Xia, Andrew Lu, Victoria Tobin

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(11), P. 2785 - 2800.e16

Published: April 23, 2024

Natural cell death pathways such as apoptosis and pyroptosis play dual roles: they eliminate harmful cells modulate the immune system by dampening or stimulating inflammation. Synthetic protein circuits capable of triggering specific programs in target could similarly remove while appropriately modulating responses. However, actively influence their modes response to natural signals, making it challenging control modes. Here, we introduce naturally inspired "synpoptosis" that proteolytically regulate engineered executioner proteins mammalian death. These direct modes, respond combinations protease inputs, selectively cells. Furthermore, synpoptosis can be transmitted intercellularly, offering a foundation for engineering synthetic killer induce desired without self-destruction. Together, these results lay groundwork programmable

Language: Английский

Citations

11
Initiator cell death event induced by SARS-CoV-2 in the human airway epithelium DOI Open Access
Kaixin Liang, Katherine C. Barnett, Martin Hsu

et al.

Science Immunology, Journal Year: 2024, Volume and Issue: 9(97)

Published: July 12, 2024

Virus-induced cell death is a key contributor to COVID-19 pathology. Cell induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) well studied in myeloid cells but less its primary host type, angiotensin-converting enzyme (ACE2)–expressing human airway epithelia (HAE). SARS-CoV-2 induces apoptosis, necroptosis, and pyroptosis HAE organotypic cultures. Single-cell limiting-dilution analysis revealed that necroptosis the event infected cells, whereas uninfected bystanders undergo occurs later during infection. Mechanistically, viral Z-RNA binding Z-DNA–binding protein 1 (ZBP1) lung tissues from patients with COVID-19. The Delta (B.1.617.2) variant, which causes more disease than Omicron (B1.1.529) humans, associated orders of magnitude–greater Z-RNA/ZBP1 interactions, severity animal models. Thus, robust ZBP1-mediated severity.

Language: Английский

Citations

11
The protease caspase-1: Activation pathways and functions DOI

Hongmin Zhen,

Yumeng Hu,

Xiaoyan Liu

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 717, P. 149978 - 149978

Published: April 23, 2024

Language: Английский

Citations

10
Dapagliflozin prevents kidney podocytes pyroptosis via miR-155-5p/HO-1/NLRP3 axis modulation DOI

Zhen-wang Zhang,

Ming-Qiu Tang,

Wu Liu

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 131, P. 111785 - 111785

Published: March 12, 2024

Language: Английский

Citations

9
Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis DOI Creative Commons
Cong Chen, Jie Wang,

Shan Zhang

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 76, P. 103321 - 103321

Published: Aug. 19, 2024

Cell death constitutes a critical component of the pathophysiology cardiovascular diseases. A growing array non-apoptotic forms regulated cell (RCD)-such as necroptosis, ferroptosis, pyroptosis, and cuproptosis-has been identified is intimately linked to various conditions. These RCD are governed by genetically programmed mechanisms within cell, with epigenetic modifications being common crucial regulatory method. Such include DNA methylation, RNA histone acetylation, non-coding RNAs. This review recaps roles modifications, RNAs in diseases, well which regulate key proteins involved death. Furthermore, we systematically catalog existing pharmacological agents targeting novel their action article aims underscore pivotal role precisely regulating specific pathways thus offering potential new therapeutic avenues that may prove more effective safer than traditional treatments.

Language: Английский

Citations

9
Donafenib activates the p53 signaling pathway in hepatocellular carcinoma, induces ferroptosis, and enhances cell apoptosis DOI Creative Commons
Jiaming Liang, Meifeng Chen, Guohong Yan

et al.

Clinical and Experimental Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 3, 2025

Donafenib is an improved version of sorafenib in which deuterium substituted into the drug's chemical structure, enhancing its stability and antitumor activity. exhibits enhanced activity better tolerance than preclinical clinical studies. However, specific mechanism effect on hepatocellular carcinoma has not been reported. Iron deposition a cell death pattern caused by disturbances iron metabolism. Apoptosis form programmed death. They may interact with each other during This study mainly explores potential donafenib activating p53 signaling pathway, inducing deposition, apoptosis carcinoma. Hepa1-6 Huh7 cells were treated various concentrations donafenib. Scratch healing pore migration tests conducted. Analyze through flow cytometry TUNEL fluorescence labeling. RNA sequencing was conducted both untreated donafenib-treated cells. The key proteins involved ferroptosis (SLC7A11, GPX4) (caspase3, caspase8, Bax, Bcl-2, p53) then evaluated using immunoblotting immunohistochemical staining. Reactive oxygen species (ROS) levels cancer measured. treatment resulted dose-dependent decrease proliferation, migration, invasion capabilities There increase rates ROS accumulation, reduction tumor volume. underwent significant changes. activates induce ferroptosis, enhance apoptosis, suggesting as effective therapeutic agent for HCC.

Language: Английский

Citations

1
PANoptosis in Bacterial Infections: A Double-Edged Sword Balancing Host Immunity and Pathogenesis DOI Creative Commons

Xiaoe He,

Xiangyan Jiang, Jiayin Guo

et al.

Pathogens, Journal Year: 2025, Volume and Issue: 14(1), P. 43 - 43

Published: Jan. 8, 2025

PANoptosis is a newly identified programmed cell death pathway that integrates characteristics of apoptosis, pyroptosis, and necroptosis. It plays dual role in the host immune response to bacterial infections. On one hand, acts as protective mechanism by inducing infected cells eliminate pathogens releasing pro-inflammatory cytokines amplify response. other bacteria can exploit evade defenses. This nature underscores potential target for developing novel therapies against review summarizes molecular mechanisms PANoptosis, along with crosstalk integration different pathways various pathogens. We also discuss roles infectious diseases, including sepsis, pulmonary infections, intestinal Elucidating underlying how manipulate this offers critical insights into host-pathogen interactions. These provide foundation designing targeted antibacterial strategies, modulating inflammation, advancing precision medicine improve clinical outcomes.

Language: Английский

Citations

1
The role of ferroptosis in colorectal cancer and its potential synergy with immunotherapy DOI Creative Commons
Wei Xia,

Yuanhao Lv,

Yan Zou

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Colorectal cancer (CRC) is one of the most prevalent and deadly malignancies worldwide. Recently, ferroptosis, a novel form regulated cell death characterized by iron dependency lipid peroxidation, has garnered significant attention from researchers. The mechanisms underlying including intracellular levels, antioxidant system regulation, offer new insights into treatment strategies. This study aims to explore emerging role ferroptosis in context immunotherapy for CRC, highlighting its potential clinical applications. We employed comprehensive review current literature elucidate biological relationship with interplay between immunotherapy. Ferroptosis reshapes tumor microenvironment (TME) regulating metabolism, systems, significantly enhancing efficacy immune checkpoint inhibitors (ICIs). Meanwhile, traditional Chinese medicine therapies promote antitumor immunity modulating TME inducing ferroptosis. Additionally, advances nanotechnology have facilitated precise therapy enabling targeted delivery inducers or immunomodulators, transforming "cold" tumors "hot" further boosting ICI efficacy. comprehensively reviews latest developments immunotherapy, medicine, importance ferroptosis-related biomarkers personalized treatment. In summary, offers promising strategy overcome CRC resistance enhance efficacy, warranting investigation translational application.

Language: Английский

Citations

1
Mitochondrial dysfunction is a major cause of thromboinflammation and inflammatory cell death in critical illnesses DOI Creative Commons
Toshiaki Iba, Julie Helms, Cheryl L. Maier

et al.

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: Jan. 13, 2025

Language: Английский

Citations

1
Resveratrol Upregulates miR‐124‐3p Expression to Target DAPK1, Regulating the NLRP3/Caspase‐1/GSDMD Pathway to Inhibit Pyroptosis and Alleviate Spinal Cord Injury DOI Creative Commons
D. Li, Yun Dai, Zhengtao Li

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(2)

Published: Jan. 1, 2025

ABSTRACT Currently, an effective treatment for spinal cord injury (SCI) is not available. Due to the irreversible primary associated with SCI, prevention and of secondary are very important. In stage, pyroptosis exacerbates deterioration injury, inhibiting beneficial recovery from SCI. The aim this study was clarify role resveratrol (RES) antipyroptotic mechanisms RES miR‐124‐3p in SCI lay a theoretical foundation clinical provide new therapeutic approaches. Using cell staining related molecular protein detection techniques assess DAPK1, effects on were investigated, injured repair rats evaluated using tissue functional experiments. vitro, DAPK1 interacts NLRP3, exerting pyroptotic effect through NLRP3/Caspase‐1/GSDMD pathway knockdown inhibits pyroptosis. miR‐124‐3P negatively regulates level reduced increased expression reduces expression, affecting vivo, GSDMD‐N levels promotes recovery, thus Therefore, we concluded that increases miR‐124‐3p, which targets pathway, alleviates

Language: Английский

Citations

1