Signaling by cGAS–STING in Neurodegeneration, Neuroinflammation, and Aging

Mitochondria-to-nucleus retrograde signaling drives formation of cytoplasmic chromatin and inflammation in senescence

(2020) Maria Grazia Vizioli et al.   GENES & DEVELOPMENT

Autolysosomal degradation of cytosolic chromatin fragments antagonizes oxidative stress–induced senescence

(2020) Xiaojuan Han et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Homeostatic regulation of STING protein at the resting state by stabilizer TOLLIP

(2020) Vladislav Pokatayev et al.   NATURE IMMUNOLOGY

VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease

(2020) Jeonghan Kim et al.   SCIENCE

LRRK2 maintains mitochondrial homeostasis and regulates innate immune responses to Mycobacterium tuberculosis

(2020) Chi G Weindel et al.   eLife

Compound C Reducing Interferon Expression by Inhibiting cGAMP Accumulation

(2020) Junzhong Lai et al.   Frontiers in Pharmacology

Inhibition of double‐strand DNA‐sensing cGAS ameliorates brain injury after ischemic stroke

(2020) Qian Li et al.   EMBO Molecular Medicine

Melatonin inhibits cytosolic mitochondrial DNA–induced neuroinflammatory signaling in accelerated aging and neurodegeneration

(2020) Abhishek Jauhari et al.   JOURNAL OF CLINICAL INVESTIGATION

Mitophagy: An Emerging Role in Aging and Age-Associated Diseases

(2020) Guo Chen et al.   Frontiers in Cell and Developmental Biology

Regulation and Consequences of cGAS Activation by Self-DNA

(2020) Christian Zierhut et al.   TRENDS IN CELL BIOLOGY

COVID-19 as a STING disorder with delayed over-secretion of interferon-beta

(2020) Jean-Marie Berthelot et al.   EBioMedicine

Cytosolic DNA Sensors and CNS Responses to Viral Pathogens

(2020) Austin M. Jeffries et al.   Frontiers in Cellular and Infection Microbiology

Discovery of GSK8612, a Highly Selective and Potent TBK1 Inhibitor

(2019) Douglas W. Thomson et al.   ACS Medicinal Chemistry Letters

Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease

(2019) Evandro F. Fang et al.   NATURE NEUROSCIENCE

Autophagy induction via STING trafficking is a primordial function of the cGAS pathway

(2019) Xiang Gui et al.   NATURE

Apoptotic Caspases Suppress Type I Interferon Production via the Cleavage of cGAS, MAVS, and IRF3

(2019) Xiaohan Ning et al.   MOLECULAR CELL

Chronic neurodegeneration induces type I interferon synthesis via STING, shaping microglial phenotype and accelerating disease progression

(2019) Arshed Nazmi et al.   GLIA

STING palmitoylation as a therapeutic target

(2019) Anne Louise Hansen et al.   Cellular & Molecular Immunology

Extranuclear DNA accumulates in aged cells and contributes to senescence and inflammation

(2019) Yuk Yuen Lan et al.   AGING CELL

SLC19A1 Is an Importer of the Immunotransmitter cGAMP

(2019) Christopher Ritchie et al.   MOLECULAR CELL

Accumulation of cytoplasmic DNA due to ATM deficiency activates the microglial viral response system with neurotoxic consequences

(2019) Xuan Song et al.   JOURNAL OF NEUROSCIENCE

CAG Repeat Not Polyglutamine Length Determines Timing of Huntington’s Disease Onset

(2019) Jong-Min Lee et al.   CELL

Cutting Edge: USP27X Deubiquitinates and Stabilizes the DNA Sensor cGAS to Regulate Cytosolic DNA–Mediated Signaling

(2019) Yunyun Guo et al.   JOURNAL OF IMMUNOLOGY

SLC19A1 transports immunoreactive cyclic dinucleotides

(2019) Rutger D. Luteijn et al.   NATURE

LRRK2 regulation of immune-pathways and inflammatory disease

(2019) Rebecca L. Wallings et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

SnapShot: Mitochondrial Nucleoid

(2018) Nina A. Bonekamp et al.   CELL

Aging, inflammation and the environment

(2018) Arsun Bektas et al.   EXPERIMENTAL GERONTOLOGY

Suramin potently inhibits cGAMP synthase, cGAS, in THP1 cells to modulate IFN-β levels

(2018) Modi Wang et al.   Future Medicinal Chemistry

BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis

(2018) Kate McArthur et al.   SCIENCE

Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA accumulation and SASP in senescent cells

(2018) Akiko Takahashi et al.   Nature Communications

A Cell-Intrinsic Interferon-like Response Links Replication Stress to Cellular Aging Caused by Progerin

(2018) Ray Kreienkamp et al.   Cell Reports

Carboxylic Acid Derivatives of Amlexanox Display Enhanced Potency toward TBK1 and IKKε and Reveal Mechanisms for Selective Inhibition

(2018) Tyler S. Beyett et al.   MOLECULAR PHARMACOLOGY

Parkin and PINK1 mitigate STING-induced inflammation

(2018) Danielle A. Sliter et al.   NATURE

Targeting STING with covalent small-molecule inhibitors

(2018) Simone M. Haag et al.   NATURE

SAMHD1 acts at stalled replication forks to prevent interferon induction

(2018) Flavie Coquel et al.   NATURE

Inflammaging: a new immune–metabolic viewpoint for age-related diseases

(2018) Claudio Franceschi et al.   Nature Reviews Endocrinology

Nitro-fatty acids are formed in response to virus infection and are potent inhibitors of STING palmitoylation and signaling

(2018) Anne Louise Hansen et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Discovery of a Novel cGAMP Competitive Ligand of the Inactive Form of STING

(2018) Tony Siu et al.   ACS Medicinal Chemistry Letters

The Cyclopeptide Astin C Specifically Inhibits the Innate Immune CDN Sensor STING

(2018) Senlin Li et al.   Cell Reports

cGAS surveillance of micronuclei links genome instability to innate immunity

(2017) Karen J. Mackenzie et al.   NATURE

Mitotic progression following DNA damage enables pattern recognition within micronuclei

(2017) Shane M. Harding et al.   NATURE

cGAS senses long and HMGB/TFAM-bound U-turn DNA by forming protein–DNA ladders

(2017) Liudmila Andreeva et al.   NATURE

Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence

(2017) Selene Glück et al.   NATURE CELL BIOLOGY

Activation of the STING-Dependent Type I Interferon Response Reduces Microglial Reactivity and Neuroinflammation

(2017) Vidhu Mathur et al.   NEURON

Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice

(2017) Jessica Vincent et al.   Nature Communications

Discovery of PF-06928215 as a high affinity inhibitor of cGAS enabled by a novel fluorescence polarization assay

(2017) Justin Hall et al.   PLoS One

RNase H2 catalytic core Aicardi-Goutières syndrome–related mutant invokes cGAS–STING innate immune-sensing pathway in mice

(2016) Vladislav Pokatayev et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Inflammatory Response in the CNS: Friend or Foe?

(2016) Marta Sochocka et al.   MOLECULAR NEUROBIOLOGY

Type I/II Interferon Balance in the Regulation of Brain Physiology and Pathology

(2016) Aleksandra Deczkowska et al.   TRENDS IN IMMUNOLOGY

Sensing of HSV-1 by the cGAS–STING pathway in microglia orchestrates antiviral defence in the CNS

(2016) Line S. Reinert et al.   Nature Communications

Non-Neuronal Cells Are Required to Mediate the Effects of Neuroinflammation: Results from a Neuron-Enriched Culture System

(2016) Chin Wai Hui et al.   PLoS One

Characterization of human disease phenotypes associated with mutations inTREX1,RNASEH2A,RNASEH2B,RNASEH2C,SAMHD1,ADAR, andIFIH1

(2015) Yanick J. Crow et al.   AMERICAN JOURNAL OF MEDICAL GENETICS PART A

The roles of CRISPR–Cas systems in adaptive immunity and beyond

(2015) Rodolphe Barrangou   CURRENT OPINION IN IMMUNOLOGY

DNA Damage Primes the Type I Interferon System via the Cytosolic DNA Sensor STING to Promote Anti-Microbial Innate Immunity

(2015) Anetta Härtlova et al.   IMMUNITY

Cutting Edge: Antimalarial Drugs Inhibit IFN-β Production through Blockade of Cyclic GMP-AMP Synthase–DNA Interaction

(2015) Jie An et al.   JOURNAL OF IMMUNOLOGY

Cutting Edge: cGAS Is Required for Lethal Autoimmune Disease in the Trex1-Deficient Mouse Model of Aicardi–Goutières Syndrome

(2015) Elizabeth E. Gray et al.   JOURNAL OF IMMUNOLOGY

Interferon-α Induces Neurotoxicity Through Activation of the Type I Receptor and the GluN2A Subunit of the NMDA Receptor

(2015) Cari F. Kessing et al.   JOURNAL OF INTERFERON AND CYTOKINE RESEARCH

Mitochondrial DNA stress primes the antiviral innate immune response

(2015) A. Phillip West et al.   NATURE

Huntington disease

(2015) Gillian P. Bates et al.   Nature Reviews Disease Primers

Apoptotic Caspases Suppress mtDNA-Induced STING-Mediated Type I IFN Production

(2014) Michael J. White et al.   CELL

Apoptotic Caspases Prevent the Induction of Type I Interferons by Mitochondrial DNA

(2014) Anthony Rongvaux et al.   CELL

The role of senescent cells in ageing

(2014) Jan M. van Deursen   NATURE

Aging-induced type I interferon response at the choroid plexus negatively affects brain function

(2014) K. Baruch et al.   SCIENCE

Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation

(2014) Huu B. Ngo et al.   Nature Communications

The Cytosolic DNA Sensor cGAS Forms an Oligomeric Complex with DNA and Undergoes Switch-like Conformational Changes in the Activation Loop

(2014) Xu Zhang et al.   Cell Reports

Dnase2a Deficiency Uncovers Lysosomal Clearance of Damaged Nuclear DNA via Autophagy

(2014) Yuk Yuen Lan et al.   Cell Reports

IFN-γ-dependent activation of the brain’s choroid plexus for CNS immune surveillance and repair

(2013) Gilad Kunis et al.   BRAIN

Type I interferon in neurological disease—The devil from within

(2013) Markus J. Hofer et al.   CYTOKINE & GROWTH FACTOR REVIEWS

Interferons in the central nervous system: A few instruments play many tunes

(2013) Trevor Owens et al.   GLIA

Oxidative Damage of DNA Confers Resistance to Cytosolic Nuclease TREX1 Degradation and Potentiates STING-Dependent Immune Sensing

(2013) Nadine Gehrke et al.   IMMUNITY

Selective TBK1/IKKi dual inhibitors with anticancer potency

(2013) Jijia Li et al.   INTERNATIONAL JOURNAL OF CANCER

The interferons and their receptors-distribution and regulation

(2012) Nicole A de Weerd et al.   IMMUNOLOGY AND CELL BIOLOGY

Progressive multiple sclerosis: The treatment gap

(2012) Courtney Humphries   NATURE

Progressive multiple sclerosis: pathology and pathogenesis

(2012) Hans Lassmann et al.   Nature Reviews Neurology

Crystal structures of STING protein reveal basis for recognition of cyclic di-GMP

(2012) Guijun Shang et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Network Organization of the Huntingtin Proteomic Interactome in Mammalian Brain

(2012) Dyna I. Shirasaki et al.   NEURON

T helper type 1 and 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis

(2010) Robert C Axtell et al.   NATURE MEDICINE

Interferon-  Causes Neuronal Dysfunction in Encephalitis

(2009) A. R. Sas et al.   JOURNAL OF NEUROSCIENCE

Viral Subversion of Apoptotic Enzymes: Escape from Death Row

(2008) Sonja M. Best   Annual Review of Microbiology

The Aging Brain

(2008) Bruce A. Yankner et al.   Annual Review of Pathology-Mechanisms of Disease

Type 1 Interferons Cool the Inflamed Brain

(2008) Robert C. Axtell et al.   IMMUNITY

Distinct and Nonredundant In Vivo Functions of IFNAR on Myeloid Cells Limit Autoimmunity in the Central Nervous System

(2008) Marco Prinz et al.   IMMUNITY

HIV-1 accessory proteins VPR and Vif modulate antiviral response by targeting IRF-3 for degradation

(2007) Atsushi Okumura et al.   VIROLOGY