Review
Biochemistry & Molecular Biology
Lee M. Booty, Clare E. Bryant
Summary: The discovery of pyroptosis and its implications in infection and immunity has provided new insights into host defense against pathogens. However, the regulation of pyroptosis is complex and varies between cell types, stimulation conditions, pathogens, and animal species. Excessive inflammation caused by pyroptosis contributes to the development of sepsis. Understanding the regulation of pyroptotic pathways is crucial for identifying potential therapeutic targets for sepsis.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Immunology
Marta Slaufova, Tugay Karakaya, Michela Di Filippo, Paulina Hennig, Hans-Dietmar Beer
Summary: Gasdermins are a family of pore-forming proteins that are involved in (auto)inflammatory diseases and cancer. They can form pores, leading to cell death and inflammation, and are closely associated with the functions of keratinocytes and the skin.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Clinical Neurology
Sebastiaan Moonen, Marta J. Koper, Evelien Van Schoor, Jolien M. Schaeverbeke, Rik Vandenberghe, Christine A. F. von Arnim, Thomas Tousseyn, Bart De Strooper, Dietmar Rudolf Thal
Summary: The study investigated the contribution of pyroptosis, a pro-inflammatory mechanism of cell death downstream of the inflammasome, to neurodegeneration in Alzheimer's disease (AD). The findings suggest the activation of pyroptosis in specific cell types and its potential link to neuron death in AD.
ACTA NEUROPATHOLOGICA
(2023)
Article
Multidisciplinary Sciences
Swarna L. Vijayaraj, Rebecca Feltham, Maryam Rashidi, Daniel Frank, Zhengyang Liu, Daniel S. Simpson, Gregor Ebert, Angelina Vince, Marco J. Herold, Andrew Kueh, Jaclyn S. Pearson, Laura F. Dagley, James M. Murphy, Andrew I. Webb, Kate E. Lawlor, James E. Vince
Summary: IL-1β is regulated by ubiquitination to prevent excessive activity, reducing inflammation and potential immunopathological damage.
NATURE COMMUNICATIONS
(2021)
Review
Immunology
Claudine S. S. Greenwood, Meghan A. A. Wynosky-Dolfi, Allison M. M. Beal, Lee M. M. Booty
Summary: The discovery of gasdermin D (GSDMD) as the terminal executioner of pyroptosis fills an important gap in our understanding of cell death and highlights the significance of the gasdermin family. GSDMD connects the innate alarm systems to an explosive, inflammatory form of cell death, triggering immunological responses in the local environment.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cardiac & Cardiovascular Systems
Xinzhe Chen, Peng-Chao Tian, Kai Wang, Man Wang, Kun Wang
Summary: Cardiovascular disease (CVD) is a common and serious health threat. Different forms of cardiomyocyte death, including apoptosis, necrosis, and pyroptosis, play important roles in the pathogenesis of CVD. Controlling cardiomyocyte pyroptosis holds promise for the treatment of cardiovascular disease.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Julia Nowowiejska, Anna Baran, Justyna Magdalena Hermanowicz, Anna Pryczynicz, Beata Sieklucka, Dariusz Pawlak, Iwona Flisiak
Summary: Psoriasis is an important issue in dermatological practice, causing both aesthetic and quality of life concerns. The pathogenesis of psoriasis remains uncertain, but GSDMD, a protein involved in cell inflammation, proliferation, and death, may play a role. The study found increased expression of GSDMD in psoriatic skin, but no significant differences in serum and urinary GSDMD concentrations between psoriasis patients and controls.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Gastroenterology & Hepatology
Itzayana Rodriguez-Antonio, Guillermo N. Lopez-Sanchez, Misael Uribe, Norberto C. Chavez-Tapia, Natalia Nuno-Lambarri
Summary: Pyroptosis is a type of programmed cell death mediated by the inflammasome through the pro-inflammatory activity of gasdermin D. Research indicates that gasdermin D plays a crucial role in connecting an elevated immune response to a sustained inflammation, linking it to the progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis. Both basic and clinical studies show evidence supporting gasdermin D as a potential therapeutic target for diseases characterized by perpetuated inflammatory processes.
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Multidisciplinary Sciences
Wen Jun Xie, Shiyu Xia, Arieh Warshel, Hao Wu
Summary: In this study, computational simulation and experimental validation were used to investigate the mechanism by which the GSDMD pore channels IL-1 release from living cells. It was found that acidic lipids effectively neutralize positive charges in the membrane-facing patches of the GSDMD pore, enabling electrostatic filtering against pro-IL-1 beta. Additionally, it was discovered that salt has an attenuating effect on electrostatic filtering. These findings provide important insights into the electrostatic influence of IL-1 transport exerted by the GSDMD pore and the impact of extrinsic factors on the electrostatic environment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Ruixuan You, Xinglan He, Zhuotong Zeng, Yi Zhan, Yangfan Xiao, Rong Xiao
Summary: Autoimmune diseases are a group of heterogeneous diseases caused by the destruction of immune tolerance and the production of autoantibodies. Excessive exacerbation of pyroptosis, a form of programmed cell death, plays a crucial role in the development of autoimmune diseases. Inflammasomes act as switches for pyroptosis, and various pyroptosis pathways disrupt immune system homeostasis and promote autoimmunity.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Xiuxia Lu, Tianhui Guo, Xing Zhang
Summary: Pyroptosis, a new form of programmed cell death, has garnered attention in cancer research. Various stimuli can trigger pyroptosis, but its role in cancer remains unclear with conflicting findings. Despite the uncertainties, pyroptosis may hold potential as a promising anti-cancer therapy.
Article
Multidisciplinary Sciences
Yingchao Hu, Yuying Jiang, Sheng Li, Xiaoqing Ma, Min Chen, Rui Yang, Shuang Wen, Paul N. Moynagh, Bingwei Wang, Gang Hu, Shuo Yang
Summary: This study reveals that GSDMD functions as a negative feedback regulator controlling inflammasome activation and provides a detailed understanding of the underlying inhibitory mechanism. These findings are important for preventing tissue damage caused by excessive inflammatory response.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Qiuyun Jiang, Zhigang Zhu, Xinliang Mao
Summary: Inflammasomes serve as a vital component in the innate immune system to defend against disruptions in homeostasis caused by pathogens or host molecules. Comprised of protein complexes, these inflammasomes assemble in the cytosol upon detection of danger signals. Activation of inflammasomes leads to the release of pro-inflammatory cytokines and pyroptotic cell death. Recent studies have highlighted the role of protein post-translational modifications, particularly ubiquitination, in modulating inflammasome activation. Understanding these mechanisms could offer new strategies for targeting diseases associated with the inflammasome pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2023)
Article
Biochemistry & Molecular Biology
Dhruv Chauhan, Dieter Demon, Lieselotte Vande Walle, Oonagh Paerewijck, Annalisa Zecchin, Leslie Bosseler, Karin Santoni, Remi Planes, Silvia Ribo, Amelie Fossoul, Amanda Goncalves, Hanne Van Gorp, Nina Van Opdenbosch, Filip Van Hauwermeiren, Etienne Meunier, Andy Wullaert, Mohamed Lamkanfi
Summary: This study confirms the presence of multiple canonical inflammasomes in neutrophils and identifies their differential roles in neutrophil immune responses. It provides new insights into the immune mechanisms of neutrophils.
Review
Immunology
Qing Kong, Zhibin Zhang
Summary: Inflammasome-activated pyroptosis (IAP) and cancer-associated pyroptosis (CAP) are both mediated by pore-forming Gasdermin (GSDM) proteins, but they differ in occurrence sites, activating mechanisms, secreting cytokines, and biological outcomes. For cancer treatment, CAP may provoke anti-tumor immunity and present a promising avenue for developing therapeutic interventions to enhance immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Sheng Li, Yuqing Wu, Dongxue Yang, Chunyan Wu, Chunmei Ma, Xue Liu, Paul N. Moynagh, Bingwei Wang, Gang Hu, Shuo Yang
JOURNAL OF EXPERIMENTAL MEDICINE
(2019)
Article
Immunology
Chunmei Ma, Sheng Li, Yingchao Hu, Yan Ma, Yuqing Wu, Chunyan Wu, Xue Liu, Bingwei Wang, Gang Hu, Jiawei Zhou, Shuo Yang
Summary: The study reveals that AIM2 plays a negative regulatory role in EAE by enhancing microglia activation and infiltration of peripheral immune cells, leading to neuroinflammation and demyelination. Additionally, AIM2 controls neuroinflammation induced by cGAS and DNA-PK through negative regulation of DNA-PK-AKT3 in microglia.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Neurosciences
Wen-Juan Rui, Sheng Li, Lin Yang, Ying Liu, Yi Fan, Ying-Chao Hu, Chun-Mei Ma, Bing-Wei Wang, Jing-Ping Shi
Summary: This study investigated the role of AIM2 in a Parkinson's disease model and found that AIM2 negatively regulates antiviral-related neuro-inflammation, reducing the development of PD. These results provide a foundation for identifying new therapeutic targets for treating PD.