Review
Biochemistry & Molecular Biology
Manoj Govindarajulu, Sindhu Ramesh, McNeil Beasley, Graham Lynn, Caleigh Wallace, Sammie Labeau, Suhrud Pathak, Rishi Nadar, Timothy Moore, Muralikrishnan Dhanasekaran
Summary: There is increasing evidence that the development of Alzheimer's disease is closely linked to immune processes, particularly neuroinflammation. The activation of the cGAS-STING signaling pathway plays a crucial role in the association between misfolded proteins and AD pathologies. Understanding the regulation of cGAS-STING activity offers potential therapeutic opportunities for modulating inflammation in CNS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Yige Huang, Bangyan Liu, Subhash C. Sinha, Sadaf Amin, Li Gan
Summary: This review summarizes the role and mechanisms of the cGAS-STING DNA-driven immune response in various neurological diseases and conditions. The article focuses on the functions of the cGAS-STING signaling pathway in various cell types of the central and peripheral nervous systems and evaluates its prospects as a therapeutic strategy.
MOLECULAR NEURODEGENERATION
(2023)
Article
Neurosciences
Guo-Liang Jiang, Xing-Long Yang, Hou-Jun Zhou, Jiang Long, Bin Liu, Lin-Ming Zhang, Di Lu
Summary: Inflammation plays a crucial role in the pathophysiology of ischemic stroke, with the cGAS-STING pathway being identified as a key player in neuroinflammation. Inhibiting the cGAS-STING pathway can reduce cell apoptosis, decrease the extent of cerebral infarction, and improve nerve function during ischemic stroke.
BRAIN RESEARCH BULLETIN
(2021)
Review
Oncology
Quanjin Li, Pu Gao
Summary: Biomolecular condensates formed by phase separation play critical roles in cGAS-STING signaling, including cGAS condensates, STING condensates, and IRF3 condensates. The regulation and activation mechanisms of these condensates are under investigation, offering new opportunities for drug discovery.
FRONTIERS OF MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Zheng Wu, Wei Tang, Fatima Elzahra E. M. Ibrahim, Xuejing Chen, Hongting Yan, Chunmei Tao, Zhiming Wang, Yunchu Guo, Yu Fu, Qi Wang, Yusong Ge
Summary: This study found that microglia-mediated neuroinflammation plays an important role in the pathogenesis of Alzheimer's disease. The expression of IFITM3 was significantly upregulated in microglia under the A beta treatment, and knockdown of IFITM3 in vitro suppressed the M1-like polarization of microglia. Moreover, IFITM3 was regulated by cGAS-STING signaling in activated microglia, and inhibition of cGAS-STING signaling reduces IFITM3 expression. In conclusion, the cGAS-STING-IFITM3 axis may be involved in A beta-induced neuroinflammation in microglia.
NEUROCHEMICAL RESEARCH
(2023)
Article
Medicine, Research & Experimental
Zhilin Hu, Xiaoyan Yu, Rui Ding, Ben Liu, Chuanjia Gu, Xiu-Wu Pan, Qiaoqiao Han, Yuerong Zhang, Jie Wan, Xin-Gang Cui, Jiayuan Sun, Qiang Zou
Summary: Activation of STING signaling in DCs is enhanced by glycolysis, leading to increased antitumor immunity. Tumor-infiltrating DCs exhibit elevated glycolytic activity, and blocking glycolysis impairs antitumor immunity. Mechanistically, glycolysis enhances ATP production, boosting STING activation and DC-mediated antitumor functions. Additionally, DC-intrinsic STING activation accelerates HIF-1 alpha-mediated glycolysis, establishing a positive feedback loop. Importantly, glycolysis facilitates STING-dependent DC activity in tissue samples from patients with non-small cell lung cancer. These findings provide insights into the crosstalk between glycolytic metabolism and STING signaling, offering potential for improving cancer therapies.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Pharmacology & Pharmacy
Chandan Chauhan, Ravinder Kumar Kaundal
Summary: Stroke is a debilitating condition with limited treatment options. Understanding the pathophysiology of stroke is crucial for developing more effective therapies. The cGAS-STING signaling pathway plays a central role in the poststroke immune response, regulating important processes such as immune cell activation, cytokine production, and tissue regeneration. Modulating this pathway shows potential in improving stroke outcomes, but challenges like specificity and off-target effects need to be addressed.
DRUG DISCOVERY TODAY
(2023)
Review
Immunology
Yuchen Yang, Li Wang, Ivonne Peugnet-Gonzalez, Daniela Parada-Venegas, Gerard Dijkstra, Klaas Nico Faber
Summary: The intestinal mucosa serves as a barrier and is involved in nutrient absorption. Genetic susceptibility and environmental factors play a critical role in the development of intestinal diseases. The innate immune system recognizes potential threats through pattern recognition receptors (PRRs), including the cGAS-STING pathway. However, the role of the cGAS-STING pathway in intestinal diseases is still debated.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Medical Laboratory Technology
Cai Lei, Ying Tan, Dan Ni, Jinfu Peng, Guanghui Yi
Summary: Double stranded DNA (dsDNA) acts as a damage-associated molecular pattern (DAMP) that triggers the body's innate immune response. The cGAS-STING pathway is involved in cell death and is closely associated with the stimulation of self-DNA and autoimmune responses. This study provides an overview of the pathway's role in ischemia or ischemia/reperfusion studies in various organs.
CLINICA CHIMICA ACTA
(2022)
Review
Cell Biology
Yuting Yang, Yiming Huang, Zhenguo Zeng
Summary: Pathogens can produce conserved pathogen-associated molecular patterns (PAMPs) that are recognized by host pattern recognition receptors (PRRs). Recent studies have shown that cytoplasmic DNA receptors can specifically recognize exogenous DNA and activate interferon 1 (IFN1), which is a significant advancement in various research fields. The cGAS-STING signaling pathway is a critical natural immune pathway in cells and plays a crucial role in pathogen infection, tumors, and various autoimmune diseases in humans.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Immunology
Nengwen Xia, Wanglong Zheng, Sen Jiang, Qi Cao, Jia Luo, Jiajia Zhang, Yulin Xu, Shaohua Sun, Kaili Zhang, Nanhua Chen, Francois Meurens, Jianzhong Zhu
Summary: This study systematically analyzed the inductions of IFN, autophagy, and apoptosis by porcine STING (pSTING) and revealed the regulatory role of autophagy on IFN and apoptosis.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Ya Liu, Feifei Pu
Summary: This article reviews the important roles of the cGAS-STING signaling pathway in natural immunity, as well as the activation process and therapeutic drugs associated with autoimmune diseases. Studying these signaling pathways is of great significance for improving the diagnosis and treatment of autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Yang Du, Zhiqiang Hu, Yien Luo, Helen Y. Wang, Xiao Yu, Rong-Fu Wang
Summary: The DNA-sensing receptor cGAS and its downstream signaling adaptor STING play crucial roles in immune defense against infectious pathogens, and the interplay between the cGAS-STING pathway and pathogens provides insight into the development of pharmacological approaches for treating infectious diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Medicine, Research & Experimental
Huashan Du, Tianmin Xu, Manhua Cui
Summary: Recent studies have revealed that the cGAS-STING pathway plays a crucial role in antitumor immunity, promoting senescence and apoptosis of cancer cells while enhancing the protective effects of cytotoxic T cells and natural killer cells. Combining the cGAS-STING signaling pathway with other therapeutic methods offers a new perspective for overcoming obstacles in its application.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Biochemistry & Molecular Biology
Xinxin Ke, Tao Hu, Mizu Jiang
Summary: The cGAS-STING signaling pathway plays a crucial role in GI inflammatory diseases and cancers. Understanding the function and mechanism of this pathway is helpful for developing therapeutic strategies.
Article
Biochemistry & Molecular Biology
Chiara Lanzillotta, Ilaria Zuliani, Chirag Vasavda, Solomon H. Snyder, Bindu D. Paul, Marzia Perluigi, Fabio Di Domenico, Eugenio Barone
Article
Multidisciplinary Sciences
Daniel Giovinazzo, Biljana Bursac, Juan Sbodio, Sumedha Nalluru, Thibaut Vignane, Adele M. Snowman, Lauren M. Albacarys, Thomas W. Sedlak, Roberta Torregrossa, Matthew Whiteman, Milos R. Filipovic, Solomon H. Snyder, Bindu D. Paul
Summary: Alzheimer's disease is characterized by memory, executive, and motor function deterioration, with neuropathological hallmarks including neurofibrillary tangles, paired helical filaments, and amyloid plaques. Dysregulation of signaling by hydrogen sulfide has been shown during aging and may play a role in preventing hyperphosphorylation of Tau in Alzheimer's disease. Furthermore, administering the H2S donor sodium GYY4137 to mouse models of Alzheimer's disease has been shown to ameliorate motor and cognitive deficits associated with the disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Geriatrics & Gerontology
Bindu Diana Paul
Summary: The reverse transsulfuration pathway is a central hub integrating the metabolism of sulfur-containing amino acids and redox homeostasis, disruption of which may have deleterious consequences and is linked to Alzheimer's disease. Potential nodes of therapeutic intervention discussed in this review may pave the way for the development of novel treatments.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Bindu D. Paul, Marian D. Lemle, Anthony L. Komaroff, Solomon H. Snyder
Summary: The review summarizes evidence of biological abnormalities in patients with acute COVID-19 and ME/CFS, including redox imbalance, systemic inflammation, neuroinflammation, impaired ATP generation, and general hypometabolism. Although these phenomena have not been extensively studied in individuals with long COVID-19, understanding these abnormalities may lead to the development of novel therapeutics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Bindu D. Paul
Summary: Huntington's disease is caused by polyglutamine repeats in the huntingtin protein, leading to toxicity by affecting cellular processes, including dysregulated organellar stress responses. The Golgi apparatus, functioning as a stress sensor, plays a crucial role in protein transport and processing, but its stress response remains largely unexplored. This review focuses on the molecular mechanisms underlying the Golgi stress response and its interaction with cysteine metabolism in the context of Huntington's disease.
Article
Biochemistry & Molecular Biology
Bindu D. Paul
Summary: Cysteine plays important roles in cellular processes and signaling cascades, and abnormal cysteine and H2S metabolism are associated with Huntington's disease.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Chirag Vasavda, Evan R. Semenza, Jason Liew, Ruchita Kothari, Ryan S. Dhindsa, Shruthi Shanmukha, Anthony Lin, Robert Tokhunts, Cristina Ricco, Adele M. Snowman, Lauren Albacarys, Francesco Pastore, Cristian Ripoli, Claudio Grassi, Eugenio Barone, Michael D. Kornberg, Xinzhong Dong, Bindu D. Paul, Solomon H. Snyder
Summary: Synapses play a crucial role in connecting neurons and transmitting information. This study investigates the role of the enzyme biliverdin reductase (BVR) in synaptic function and plasticity. The findings suggest that BVR acts as a bridge between key signaling molecules in synaptic adhesion pathways, and its absence leads to deficits in learning and memory.
Article
Medicine, Research & Experimental
Yvonne L. Latour, Johanna C. Sierra, Jordan L. Finley, Mohammad Asim, Daniel P. Barry, Margaret M. Allaman, Thaddeus M. Smith, Kara M. McNamara, Paula B. Luis, Claus Schneider, Justin Jacobse, Jeremy A. Goettel, M. Wade Calcutt, Kristie L. Rose, Kevin L. Schey, Ginger L. Milne, Alberto G. Delgado, M. Blanca Piazuelo, Bindu D. Paul, Solomon H. Snyder, Alain P. Gobert, Keith T. Wilson
Summary: Macrophages play a crucial role in the inflammatory response to Helicobacter pylori infection. Induction of cystathionine gamma-lyase (CTH) in macrophages by H. pylori promotes persistent inflammation. CTH deficiency results in altered macrophage function and metabolism, leading to decreased gastric inflammation.
Article
Multidisciplinary Sciences
Chirag Vasavda, Risheng Xu, Jason Liew, Ruchita Kothari, Ryan S. Dhindsa, Evan R. Semenza, Bindu D. Paul, Dustin P. Green, Mark F. Sabbagh, Joseph Y. Shin, Wuyang Yang, Adele M. Snowman, Lauren K. Albacarys, Abhay Moghekar, Carlos A. Pardo-Villamizar, Mark Luciano, Judy Huang, Chetan Bettegowda, Shawn G. Kwatra, Xinzhong Dong, Michael Lim, Solomon H. Snyder
Summary: Trigeminal neuralgia is a highly painful neurological condition that currently has limited treatment options. A study found that patients with this condition have increased levels of reactive oxygen species, which can activate pain-transducing channels. By stimulating the NRF2 antioxidant transcriptional network, researchers were able to reduce pain by reversing the oxidative stress. They also identified two potential drug candidates through transcriptome-guided analysis, one of which is already FDA-approved.
Article
Biochemistry & Molecular Biology
Bindu D. Paul, Juan I. Sbodio, Solomon H. Snyder
Summary: This study found that cysteine metabolism is compromised at both transcriptional and post-translational levels in Huntington's disease, indicating that restoring cysteine homeostasis may be beneficial in treating this neurodegenerative disorder.
Editorial Material
Biochemistry & Molecular Biology
Bindu D. Paul
Summary: Although women are at higher risk for Alzheimer's disease and other tauopathies, the underlying mechanisms are unclear. In this issue of Cell, Yan et al. show that aberrantly high activity of X-linked USP11 deubiquitinase in women impairs clearance of tau, the principal component of neurofibrillary tangles in Alzheimer's disease.
Review
Biochemistry & Molecular Biology
Bindu D. Paul, Andrew A. Pieper
Summary: The gaseous signaling molecule hydrogen sulfide (H2S) plays a critical role in regulating various physiological processes, including stress responses and neuromodulatory effects that are often disrupted in aging, disease, and injury. H2S is particularly important for maintaining neuronal health and survival, both in normal and pathological conditions. It exerts its effects by modifying target proteins through persulfidation/sulfhydration of reactive cysteine residues. This article reviews the latest findings on the neuroprotective roles of H2S in Alzheimer's disease (AD) and traumatic brain injury, which is a major risk factor for AD.
Article
Biochemical Research Methods
Chirag Vasavda, Solomon H. Snyder, Bindu D. Paul
Summary: Evaluating redox homeostasis by measuring levels of ROS and RNS in brain slices provides a comprehensive picture of neural redox signaling, with the brain being particularly vulnerable to excessive ROS and RNS.
Article
Biochemistry & Molecular Biology
Chirag Vasavda, Ruchita Kothari, Adarsha P. Malla, Robert Tokhunts, Anthony Lin, Ming Ji, Cristina Ricco, Risheng Xu, Harry G. Saavedra, Juan I. Sbodio, Adele M. Snowman, Lauren Albacarys, Lynda Hester, Thomas W. Sedlak, Bindu D. Paul, Solomon H. Snyder
CELL CHEMICAL BIOLOGY
(2019)
