Article
Biology
Eijaz Ahmed Bhat, Nasreena Sajjad, Javeed Ahmad Tantray, Yan-Yan Hor, Irfan A. Rather
Summary: The formation of inflammasome complexes contributes to the activation of inflammatory caspases, and different constructs study showed stability and interactions under physiological conditions. The results indicate that POP3 forms a dimer, ASC PYD domain can self-oligomerize, but inhibits complex formation with POP3.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Multidisciplinary Sciences
Ivo M. Glueck, Grusha Primal Mathias, Sebastian Strauss, Virgile Rat, Irene Gialdini, Thomas Sebastian Ebert, Che Stafford, Ganesh Agam, Suliana Manley, Veit Hornung, Ralf Jungmann, Christian Sieben, Don C. Lamb
Summary: In this study, the structure of ASC specks following activation of the NLRP3 inflammasome was visualized using dual-color 3D super-resolution imaging techniques. The ASC speck consists of a dense core and emerging filaments, with a diameter varying between 800 and 1000 nm. The ASC speck does not colocalize with the microtubule-organizing center.
Article
Multidisciplinary Sciences
Inga Hochheiser, Heide Behrmann, Gregor Hagelueken, Juan F. Rodriguez-Alcazar, Anja Kopp, Eicke Latz, Elmar Behrmann, Matthias Geyer
Summary: In this study, the cryo-EM structure of the human NLRP3(PYD) filament was determined, and a characteristic structure of the filament ends was identified. It was found that the ASC adaptor protein only interacts with the B-end of the filament. A molecular model of the ASC speck consisting of active NLRP3, ASC, and Caspase-1 proteins was proposed.
Article
Biochemistry & Molecular Biology
Muhammad Riaz, Ashfaq Ur Rehman, Shahid Ali Shah, Humaira Rafiq, Shaoyong Lu, Yingying Qiu, Abdul Wadood
Summary: The NLRP3-PYD inflammasome activates an inflammatory pathway in response to cell damage or infections, with dysregulation leading to chronic inflammation and autoimmune disorders. Computational approaches were used to study the interactions of NLRP3 and ASC PYD domains involved in inflammasome complex activation. The research sheds light on the molecular mechanisms of inflammasome and offers insights into drug discovery processes.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Biochemical Research Methods
Mohsen Isazadeh, Mojdeh Amandadi, Farnaz Haghdoust, Shima Lotfollazadeh, Mar Orzaez, Saman Hosseinkhani
Summary: This study used the split luciferase complementation assay to investigate the interactions of NLRP3 during inflammasome formation. By mutating the phosphomimetic residue at the interface of NLRP3 interactions, the designed biosensor was able to monitor the NLRP3PYD-NLRP3PYD interaction in vitro. This assay provides a specific method to study the PYD-PYD interaction and can be used to screen chemicals and drugs.
ANALYTICAL BIOCHEMISTRY
(2022)
Article
Immunology
Lucia de Almeida, Savita Devi, Mohanalaxmi Indramohan, Qi-Quan Huang, Rojo A. Ratsimandresy, Richard M. Pope, Andrea Dorfleutner, Christian Stehlik
Summary: Canonical inflammasomes are innate immune protein scaffolds that activate inflammatory responses. Excessive activation of inflammasomes is associated with inflammatory diseases. This study found that the protein POP1 regulates the inflammatory response in gout and functions by interfering with crucial interactions within the inflammasome complex.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Savita Devi, Mohanalaxmi Indramohan, Elisabeth Jager, Jessica Carriere, Lan H. Chu, Lucia de Almeida, David R. Greaves, Christian Stehlik, Andrea Dorfleutner
Summary: Inflammatory responses are important for controlling infections and tissue repair, but excessive inflammation can cause inflammatory disease. Pro-inflammatory cytokines IL-1b and IL-18 depend on caspase-1 activation within inflammasomes. Higher primates have evolved small proteins (POPs and COPs) to limit inflammation by targeting crucial interactions. This study shows that COPs can regulate inflammasome activation by modulating CARD interactions and ameliorate inflammatory disease.
Article
Biochemistry & Molecular Biology
Xin Tang, Xiande Liu, Zhiyong Wang, Meiling Chen, Dongling Zhang
Summary: This study identified an ASC gene in the large yellow croaker and investigated its expression characteristics and related signal pathways. The highest expression of LcASC was observed in the spleen, followed by the gills and skin. It also showed induced expressions in response to immune stimulation, especially Vibrio Parahaemolyticus infection. Comparative transcriptome analysis revealed differentially expressed genes in LcASC overexpressed cells, with Fos and DOK3 playing important roles in the immune system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Fatima Martin-Sanchez, Vincent Compan, Alejandro Penin-Franch, Ana Tapia-Abellan, Ana I. I. Gomez, Maria C. Banos-Gregori, Florian I. I. Schmidt, Pablo Pelegrin
Summary: The structure of the inflammasome oligomer formed by ASC protein could change in conditions of low intracellular K+, allowing for increased recruitment of pro-caspase-1. This finding highlights the importance of the inflammasome in the inflammatory response and suggests that decreased intracellular K+ can enhance the recruitment of pro-caspase-1 into ASC specks.
JOURNAL OF CELL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jaromir Tomasik, Grzegorz Wladyslaw Basak
Summary: Inflammasomes are intracellular complexes that play an important role in promoting inflammatory responses and have been associated with various diseases. Recent studies have focused on their contribution to hematological diseases, with specific inflammasomes being linked to different types of blood cancers. Gene variants of inflammasomes have also been linked to disease susceptibility. Although the understanding of inflammasomes is still incomplete, the available results provide a valuable basis for clinical applications and potential breakthroughs in innovative treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Senquan Wu, Jia Liao, Guodong Hu, Liang Yan, Xingyu Su, Jiezhou Ye, Chanjuan Zhang, Tian Tian, Huadong Wang, Yiyang Wang
Summary: This study found that Corilagin has a protective effect against LPS-induced sepsis by inhibiting pyroptosis and NLRP3 inflammasome activation. The experimental results show that Corilagin can prolong the survival time of septic mice, attenuate multi-organ injury, and act by interfering with the TLR4-MyD88 interaction and downregulating genes associated with inflammatory responses.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Mitsuhito Koizumi, Takao Watanabe, Junya Masumoto, Kotaro Sunago, Yoshiki Imamura, Kozue Kanemitsu, Teru Kumagi, Yoichi Hiasa
Summary: ASC plays a crucial role in PDAC progression and poor prognosis, with its high expression associated with altered cell cycle regulation and tumor growth inhibition.
SCIENTIFIC REPORTS
(2021)
Article
Food Science & Technology
Hongxia Li, Lin Xiao, Hui He, Hongmei Zeng, Jingjing Liu, Chunjie Jiang, Guibin Mei, Jiasheng Yu, Hao Chen, Ping Yao, Yuhan Tang
Summary: This study investigates the anti-atherosclerotic properties of quercetin by modulating the Gal-3-NLRP3 pathway, showing promising effects in reducing atherosclerotic lesions. The findings suggest a potential strategy for the prevention and treatment of atherosclerosis using naturally-occurring quercetin.
MOLECULAR NUTRITION & FOOD RESEARCH
(2021)
Article
Cell Biology
Tae-Geun Yu, Jeong Seok Cha, Gijeong Kim, Yoo-Kyoung Sohn, Youngki Yoo, Uijin Kim, Ji-Joon Song, Hyun-Soo Cho, Hak-Sung Kim
Summary: Inflammasomes are multi-protein complexes that play a crucial role in host defense against pathogens. The oligomerization degrees of ASC specks regulate caspase-1 activation in the extracellular space.
CELL DEATH DISCOVERY
(2023)
Article
Cell Biology
Ping Wang, Yulan Gu, Jianke Yang, Jiamin Qiu, Yeqiong Xu, Zengxiang Xu, Jiguang Gao, Chuandan Wan
Summary: Inflammasomes play an important role in the development of gastric cancer and immune regulation. Elevated expression of NLRP1/NLRP3 is associated with poor prognosis and immune cell infiltration in gastric cancer. NLRP1 and NLRP3 may participate in the same immune-related pathways.
Article
Cardiac & Cardiovascular Systems
Manon Viaud, Stoyan Ivanov, Nemanja Vujic, Madalina Duta-Mare, Lazaro-Emilio Aira, Thibault Barouillet, Elsa Garcia, Francois Orange, Isabelle Dugail, Isabelle Hainault, Christian Stehlik, Sandrine Marchetti, Laurent Boyer, Rodolphe Guinamard, Fabienne Foufelle, Andrea Bochem, Kees G. Hovingh, Edward B. Thorp, Emmanuel L. Gautier, Dagmar Kratky, Paul Dasilva-Jardine, Laurent Yvan-Charvet
CIRCULATION RESEARCH
(2018)
Review
Biochemistry & Molecular Biology
Mohanalaxmi Indramohan, Christian Stehlik, Andrea Dorfleutner
JOURNAL OF MOLECULAR BIOLOGY
(2018)
Meeting Abstract
Cardiac & Cardiovascular Systems
S. Ivanov, M. Viaud, N. Vujic, M. Duta-Mare, I. Dugail, I. Hainault, C. Stehlik, S. Marchetti, L. Boyer, R. Guinamard, F. Foufelle, A. Bochem, K. G. Hovingh, E. B. Thorp, E. L. Gautier, D. Kratky, L. Yvan-Charvet
Review
Biochemistry & Molecular Biology
Savita Devi, Christian Stehlik, Andrea Dorfleutner
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Review
Biochemistry & Molecular Biology
Kevin P. Downs, Huyen Nguyen, Andrea Dorfleutner, Christian Stehlik
MOLECULAR ASPECTS OF MEDICINE
(2020)
Article
Multidisciplinary Sciences
Jargalsaikhan Dagvadorj, Karolina Mikulska-Ruminska, Gantsetseg Tumurkhuu, Rojo A. Ratsimandresy, Jessica Carriere, Allen M. Andres, Stefanie Marek-Iannucci, Yang Song, Shuang Chen, Malcolm Lane, Andrea Dorfleutner, Roberta A. Gottlieb, Christian Stehlik, Suzanne Cassel, Fayyaz S. Sutterwala, Ivet Bahar, Timothy R. Crother, Moshe Arditi
Summary: The balance between NLRP3 inflammasome activation and mitophagy is crucial for cellular homeostasis, with IL-1 alpha playing a key role in regulating this balance. IL-1 alpha deficiency can lead to altered cellular functions and health by affecting mitochondrial damage and NLRP3 inflammasome activation. The interaction between IL-1 alpha and mitochondrial cardiolipin disrupts mitophagy and enhances NLRP3 inflammasome activation, highlighting the importance of this regulatory mechanism in cellular health.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Immunology
Jessica Carriere, Andrea Dorfleutner, Christian Stehlik
Summary: NOD-like receptors are cytosolic pattern recognition receptors that play a role in innate immune response. Activation of NLRs results in the assembly of inflammasomes, which are responsible for the release of pro-inflammatory cytokines. NLRP7 mutations have been linked to reproductive diseases, particularly molar pregnancy, but the specific molecular mechanisms are still largely unknown.
Article
Immunology
Anu Gangopadhyay, Savita Devi, Shivendra Tenguria, Jessica Carriere, Huyen Nguyen, Elisabeth Jager, Hemisha Khatri, Lan H. Chu, Rojo A. Ratsimandresy, Andrea Dorfleutner, Christian Stehlik
Summary: The study reveals that NLRP11 is a crucial component of the NLRP3 inflammasome in human macrophages, and its absence prevents inflammasome activation and immune response. This research is of great significance in uncovering the mechanisms of inflammasome regulation.
Article
Cell Biology
Savita Devi, Mohanalaxmi Indramohan, Elisabeth Jager, Jessica Carriere, Lan H. Chu, Lucia de Almeida, David R. Greaves, Christian Stehlik, Andrea Dorfleutner
Summary: Inflammatory responses are important for controlling infections and tissue repair, but excessive inflammation can cause inflammatory disease. Pro-inflammatory cytokines IL-1b and IL-18 depend on caspase-1 activation within inflammasomes. Higher primates have evolved small proteins (POPs and COPs) to limit inflammation by targeting crucial interactions. This study shows that COPs can regulate inflammasome activation by modulating CARD interactions and ameliorate inflammatory disease.
Meeting Abstract
Immunology
Lan H. Chu, Mohanalaxmi Indramohan, Rojo A. Ratsimandresy, Anu Gangopadhyay, Emily P. Morris, Denise M. Monack, Andrea Dorfleutner, Christian Stehlik
JOURNAL OF IMMUNOLOGY
(2018)
Article
Medicine, Research & Experimental
Swati Bhattacharyya, Wenxia Wang, Wenyi Qin, Kui Cheng, Sara Coulup, Sherry Chavez, Shuangshang Jiang, Kirtee Raparia, Lucia Maria V. De Almeida, Christian Stehlik, Zenshiro Tamaki, Hang Yin, John Varga