Evidence
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
J Clin Invest. 2024 Jan 9;134(4):e169562. doi: 10.1172/JCI169562.
ABSTRACT
Chronic and elevated levels of the antiviral cytokine IFN-α in the brain are neurotoxic. This is best observed in patients with genetic cerebral interferonopathies such as Aicardi-Goutières syndrome. Cerebral interferonopathies typically manifest in early childhood and lead to debilitating disease and premature death. There is no cure for these diseases with existing treatments largely aimed at managing symptoms. Thus, an effective therapeutic strategy is urgently needed. Here, we investigated the effect of antisense oligonucleotides targeting the murine IFN-α receptor (Ifnar1 ASOs) in a transgenic mouse model of cerebral interferonopathy. Intracerebroventricular injection of Ifnar1 ASOs into transgenic mice with brain-targeted chronic IFN-α production resulted in a blunted cerebral interferon signature, reduced neuroinflammation, restoration of blood-brain barrier integrity, absence of tissue destruction, and lessened neuronal damage. Remarkably, Ifnar1 ASO treatment was also effective when given after the onset of neuropathological changes, as it reversed such disease-related features. We conclude that ASOs targeting the IFN-α receptor halt and reverse progression of IFN-α-mediated neuroinflammation and neurotoxicity, opening what we believe to be a new and promising approach for the treatment of patients with cerebral interferonopathies.
PMID:38357922 | DOI:10.1172/JCI169562
![Google](https://www.google.com/images/branding/googlelogo/2x/googlelogo_light_color_92x30dp.png)
![Google Keep](https://www.gstatic.com/images/branding/product/1x/keep_48dp.png)
![Share on Linkedin](https://psychiatryai.com/wp-content/uploads/2023/10/linkedin-logo-png-2048-1.png)
Estimated reading time: 4 minute(s)
Latest: Psychiatryai.com #RAISR4D Evidence
![](/wp-content/uploads/2024/04/bd462cc11bcf0bd0d0d6f1d0f8b7cd04-modified-1.png)
Cool Evidence: Engaging Young People and Students in Real-World Evidence
![](/wp-content/uploads/2024/04/bd462cc11bcf0bd0d0d6f1d0f8b7cd04-modified-1.png)
Real-Time Evidence Search [Psychiatry]
![](/wp-content/uploads/2024/04/pubmed.png)
AI Research
![](/wp-content/uploads/2024/05/Il5nR_nf_400x400-modified-1.png)
Interferon-a receptor antisense oligonucleotides reduce neuroinflammation and neuropathology in a mouse model of cerebral interferonopathy
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
🌐 90 Days
AI Virtual Reality Related Evidence Matrix
Effects of local reduction of endogenous α-synuclein using antisense oligonucleotides on the fibril-induced propagation of pathology through the neural network in wild-type mice Regulation of human microglial gene expression and function via RNAase-H active antisense oligonucleotides in vivo in Alzheimer's disease Oral administration of IPI549 protects mice from neuropathology and an overwhelming inflammatory response during experimental cerebral malaria Neuroprotective Efficacy of the Glucocorticoid Receptor Modulator PT150 in the Rotenone Mouse Model of Parkinson's Disease Pathophysiology of cerebral small vessel disease: a journey through recent discoveries Protocol for inducing severe Scn2a insufficiency in mice by intracerebroventricular antisense oligonucleotide injection Peripheral vascular dysfunction and the aging brain Immunotherapy with an antibody against CD1d modulates neuroinflammation in an a-synuclein transgenic model of Lewy body like disease Induction of SK-MEL-28 Invasion by Brain Cortical Cell-Conditioned Medium Through CXCL10 Signaling Quantifying the activity profile of ASO and siRNA conjugates in glioblastoma xenograft tumors in vivo Cardiac output-mediated regulation of cerebral blood flow during exercise: Clinical perspectives on the indirect impact of muscle metaboreflex Making sense of Timothy syndrome with 3D human neuronal models Early Impairment of Cerebral Bioenergetics After Cardiopulmonary Bypass in Neonatal Swine Antisense oligonucleotide therapeutic approach for Timothy syndrome Failure of C9orf72 sense repeat-targeting antisense oligonucleotides: lessons learned and the path forward Failure of C9orf72 sense repeat-targeting antisense oligonucleotides: lessons learned and the path forward Failure of C9orf72 sense repeat-targeting antisense oligonucleotides: lessons learned and the path forward Clinical outcome of a branch-first approach with a novel continuous whole-brain perfusion strategy for total arch surgery Tcf4 dysfunction alters dorsal and ventral cortical neurogenesis in Pitt-Hopkins syndrome mouse model showing sexual dimorphism The advent of RNA-based therapeutics for metabolic syndrome and associated conditions: a comprehensive review of the literature Regulating NCOA4-Mediated Ferritinophagy for Therapeutic Intervention in Cerebral Ischemia-Reperfusion Injury Lipid nanoparticle-encapsulated lncRNA DLX6-AS1 knockdown ameliorates cerebral ischemic injury via the Nrf2/HO-1/NLRP3 axis Cerebral venous congestion alters CNS homeostatic plasticity, evoking tinnitus-like behavior Disturbance in cerebral blood microcirculation and hypoxic-ischemic microenvironment are associated with the development of brain metastasis Disturbance in cerebral blood microcirculation and hypoxic-ischemic microenvironment are associated with the development of brain metastasis Rejuvenation of peripheral immune cells attenuates Alzheimer's disease-like pathologies and behavioral deficits in a mouse model The Sirtuin 5 Inhibitor MC3482 Ameliorates Microglia‑induced Neuroinflammation Following Ischaemic Stroke by Upregulating the Succinylation Level of Annexin-A1 The Sirtuin 5 Inhibitor MC3482 Ameliorates Microglia‑induced Neuroinflammation Following Ischaemic Stroke by Upregulating the Succinylation Level of Annexin-A1 Soluble Epoxide Hydrolase Inhibition Reverses Cognitive Dysfunction in a Mouse Model of Metabolic Syndrome by Modulating Inflammation Molecular signatures in prion disease: altered death receptor pathways in a mouse model Targeting the Hippo pathway to prevent radioresistance brain metastases from the lung (Review) P2Y1 receptor in Alzheimer's disease Mortality, cardiac and cerebral damages reduction by IL-1 inhibition in a murine model of TTP SLC22A17 as a Cell Death-Linked Regulator of Tight Junctions in Cerebral Ischemia Protective effect of PDE4B subtype-specific inhibition in an App knock-in mouse model for Alzheimer's disease Regional cerebral blood flow in a patient with asystole episodes associated with anti-NMDA receptor encephalitis Estimation of the Ischemic Lesion in the Experimental Stroke Studies Using Magnetic Resonance Imaging (Review) Therapeutic effects of orexin-A in sepsis-associated encephalopathy in mice Longitudinal cerebral perfusion in presymptomatic genetic frontotemporal dementia: GENFI results Estimation of the Ischemic Lesion in the Experimental Stroke Studies Using Magnetic Resonance Imaging (Review) Ion transporter cascade, reactive astrogliosis and cerebrovascular diseases Modelling midline shift and ventricle collapse in cerebral oedema following acute ischaemic stroke Modelling midline shift and ventricle collapse in cerebral oedema following acute ischaemic stroke BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy Efficacy of bumetanide in animal models of ischemic stroke: a systematic review and meta-analysis Imaging neuroinflammation in individuals with substance use disorders A comprehensive review on the development of sporadic cerebral arteriovenous malformations: from Padget to next-generation sequencing Epigenetic alterations in creatine transporter deficiency: a new marker for dodecyl creatine ester therapeutic efficacy monitoring Cerebral oxygen metabolism and brain electrical activity of healthy full-term neonates in high-altitude areas: a multicenter clinical research protocol Electro-scalp acupuncture regulates the expression of CYP27a1/b1, CYP24a and related inflammatory cytokines in ischemic cortex of rats with middle cerebral artery occlusion Electro-scalp acupuncture regulates the expression of CYP27a1/b1, CYP24a and related inflammatory cytokines in ischemic cortex of rats with middle cerebral artery occlusion Intravenous administration of anti-CD47 antibody augments hematoma clearance, mitigates acute neuropathology, and improves cognitive function in a rat model of penetrating traumatic brain injury Differential Regulation of Neurotrophic Factors During Pathogenic Tau-Aggregation in a Tau Transgenic Mouse Model for Alzheimer's Disease: A Protocol for Double-Labeling mRNA by In Situ Hybridization and Protein Epitopes by Immunohistochemistry Therapeutic potential of Thai herbal formula for cognitive impairment: A metabolomics approach for Comprehensive Insights Limb-Clasping Response in NMDA Receptor Palmitoylation-Deficient Mice Comprehensive mapping of histamine H(1) receptor mRNA in the mouse brain Discovery of Potential Drug Targeting Key Genes in Alzheimer's Disease: Insights from Transcriptome Analysis and Molecular Docking Shared inflammatory glial cell signature after stab wound injury, revealed by spatial, temporal, and cell-type-specific profiling of the murine cerebral cortex Regulation of cerebral blood flow boosts precise brain targeting of vinpocetine-derived ionizable-lipidoid nanoparticles The lncRNA Malat1 is trafficked to the cytoplasm as a localized mRNA encoding a small peptide in neurons CXCL10 is a crucial chemoattractant for efficient intranasal delivery of mesenchymal stem cells to the neonatal hypoxic-ischemic brain Mild Hypoxia Accelerates Cerebral Cavernous Malformation Disease Through CX3CR1-CX3CL1 Signaling Mild Hypoxia Accelerates Cerebral Cavernous Malformation Disease Through CX3CR1-CX3CL1 Signaling Shining a light on cerebral autoregulation: Are we anywhere near the truth?
Evidence Blueprint
Interferon-a receptor antisense oligonucleotides reduce neuroinflammation and neuropathology in a mouse model of cerebral interferonopathy
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
☊ AI-Driven Related Evidence Nodes
(recent articles with at least 5 words in title)
More Evidence
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
Interferon-a receptor antisense oligonucleotides reduce neuroinflammation and neuropathology in a mouse model of cerebral interferonopathy
🌐 365 Days
AI Virtual Reality Related Evidence Matrix
Secreted LRPAP1 binds and triggers IFNAR1 degradation to facilitate virus evasion from cellular innate immunity Effects of local reduction of endogenous α-synuclein using antisense oligonucleotides on the fibril-induced propagation of pathology through the neural network in wild-type mice Regulation of human microglial gene expression and function via RNAase-H active antisense oligonucleotides in vivo in Alzheimer's disease Treatment of the CRND8 mouse model for cerebral amyloid angiopathy, exhibited increased levels of neuron specific enolase in brain tissue following long-term treatment with a modified C5a receptor agonist, accompanied by improved cognitive function Ultrasound-Targeted Microbubble Destruction Increases BBB Permeability and Promotes Stem Cell-Induced Regeneration of Stroke by Downregulating MMP8 Brain expression profiles of two SCN1A antisense RNAs in children and adolescents with epilepsy Advanced Magnetic Resonance Imaging (MRI) to Define the Microvascular Injury Driven by Neuroinflammation in the Brain of a Mouse Model of Hypertension Oral administration of IPI549 protects mice from neuropathology and an overwhelming inflammatory response during experimental cerebral malaria Hypoxic oligodendrocyte precursor cell-derived VEGFA is associated with blood-brain barrier impairment Ischemia-Reperfusion Programming of Alzheimer's Disease-Related Genes-A New Perspective on Brain Neurodegeneration after Cardiac Arrest Neuroprotective Efficacy of the Glucocorticoid Receptor Modulator PT150 in the Rotenone Mouse Model of Parkinson's Disease Selective neuroimmune modulation by type I interferon drives neuropathology and neurologic dysfunction following traumatic brain injury Pathophysiology of cerebral small vessel disease: a journey through recent discoveries Evaluation of Antisense Oligonucleotides Therapy Targeting Hsd17b13 in a Fibrosis Mice Model Heterozygous mutations in the C-terminal domain of COPA underlie a complex autoinflammatory syndrome Protocol for inducing severe Scn2a insufficiency in mice by intracerebroventricular antisense oligonucleotide injection A common single nucleotide variant in the cytokine receptor-like factor-3 (CRLF3) gene causes neuronal deficits in human and mouse cells The role of serum/glucocorticoid-regulated kinase 1 in brain function following cerebral ischemia Peripheral vascular dysfunction and the aging brain Immunotherapy with an antibody against CD1d modulates neuroinflammation in an a-synuclein transgenic model of Lewy body like disease Induction of SK-MEL-28 Invasion by Brain Cortical Cell-Conditioned Medium Through CXCL10 Signaling IFNγ drives neuroinflammation, demyelination, and neurodegeneration in a mouse model of multiple system atrophy Cerebral vasculitis as a clinical manifestation of neurosarcoidosis: A scoping review Quantifying the activity profile of ASO and siRNA conjugates in glioblastoma xenograft tumors in vivo Cardiac output-mediated regulation of cerebral blood flow during exercise: Clinical perspectives on the indirect impact of muscle metaboreflex Activation of TNF Receptor 2 Improves Synaptic Plasticity and Enhances Amyloid-β Clearance in an Alzheimer's Disease Mouse Model with Humanized TNF Receptor 2 Making sense of Timothy syndrome with 3D human neuronal models Preclinical Evidence for the Glucocorticoid-Sparing Potential of a Dual Toll-Like Receptor 7/8 Inhibitor in Autoimmune Diseases Early Impairment of Cerebral Bioenergetics After Cardiopulmonary Bypass in Neonatal Swine Hippocampal glial inflammatory markers are differentially altered in a novel mouse model of perimenopausal cerebral amyloid angiopathy Inhibiting CSF1R alleviates cerebrovascular white matter disease and cognitive impairment Antisense oligonucleotide therapeutic approach for Timothy syndrome Failure of C9orf72 sense repeat-targeting antisense oligonucleotides: lessons learned and the path forward Failure of C9orf72 sense repeat-targeting antisense oligonucleotides: lessons learned and the path forward Failure of C9orf72 sense repeat-targeting antisense oligonucleotides: lessons learned and the path forward Clinical outcome of a branch-first approach with a novel continuous whole-brain perfusion strategy for total arch surgery Tcf4 dysfunction alters dorsal and ventral cortical neurogenesis in Pitt-Hopkins syndrome mouse model showing sexual dimorphism TMEM2 suppresses TLR3-mediated IFN-β/ISG56/CXCL10 expression in BEAS-2B bronchial epithelial cells The advent of RNA-based therapeutics for metabolic syndrome and associated conditions: a comprehensive review of the literature Repeated mild traumatic brain injury triggers pathology in asymptomatic C9ORF72 transgenic mice Regulating NCOA4-Mediated Ferritinophagy for Therapeutic Intervention in Cerebral Ischemia-Reperfusion Injury The Effect of Fat Intake with Increased Omega-6-to-Omega-3 Polyunsaturated Fatty Acid Ratio in Animal Models of Early and Late Alzheimer's Disease-like Pathogenesis Generation of mouse hippocampal brain organoids from primary embryonic neural stem cells Increased Expression of Transferrin Receptor 1 in the Brain Cortex of 5xFAD Mouse Model of Alzheimer's Disease Is Associated with Activation of HIF-1 Signaling Pathway Lipid nanoparticle-encapsulated lncRNA DLX6-AS1 knockdown ameliorates cerebral ischemic injury via the Nrf2/HO-1/NLRP3 axis Neuroprotective effects of ivermectin against transient cerebral ischemia-reperfusion in rats Genetic reduction of insulin signaling mitigates amyloid-β deposition by promoting expression of extracellular matrix proteins in the brain Treatment of pediatric cerebral radiation necrosis using hyperbaric oxygenation In Vivo Intracerebral Administration of α-Ketoisocaproic Acid to Neonate Rats Disrupts Brain Redox Homeostasis and Promotes Neuronal Death, Glial Reactivity, and Myelination Injury Uncoupling of Ca2+ sparks from BK channels in cerebral arteries underlies hypoperfusion in hypertension-induced vascular dementia Establishment of a Murine Chronic Anorexia Nervosa Model Advancements in investigating the role of cerebral small vein loss in Alzheimer's disease-related pathological changes Cerebral venous congestion alters CNS homeostatic plasticity, evoking tinnitus-like behavior Genetic deletion of astrocytic calcineurin B1 prevents cognitive impairment and neuropathology development in acute and chronic mouse models of Alzheimer's disease Myeloid and lymphoid expression of C9orf72 regulates IL-17A signaling in mice Disturbance in cerebral blood microcirculation and hypoxic-ischemic microenvironment are associated with the development of brain metastasis Disturbance in cerebral blood microcirculation and hypoxic-ischemic microenvironment are associated with the development of brain metastasis Chronic administration of XBD173 ameliorates cognitive deficits and neuropathology via 18 kDa translocator protein (TSPO) in a mouse model of Alzheimer's disease Rejuvenation of peripheral immune cells attenuates Alzheimer's disease-like pathologies and behavioral deficits in a mouse model The Sirtuin 5 Inhibitor MC3482 Ameliorates Microglia‑induced Neuroinflammation Following Ischaemic Stroke by Upregulating the Succinylation Level of Annexin-A1 The Sirtuin 5 Inhibitor MC3482 Ameliorates Microglia‑induced Neuroinflammation Following Ischaemic Stroke by Upregulating the Succinylation Level of Annexin-A1 Non-classical monocytes promote neurovascular repair in cerebral small vessel disease associated with microinfarctions via CX3CR1 Cerebrospinal fluid inflammatory cytokine profiles of patients with neurotropic parasitic infections Soluble Epoxide Hydrolase Inhibition Reverses Cognitive Dysfunction in a Mouse Model of Metabolic Syndrome by Modulating Inflammation