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- A Brainwide Atlas of Synapses Across the Mouse Life Span
- A Circadian Rhythm-Gated Subcortical Pathway for Nighttime-Light-Induced Depressive-Like Behaviors in Mice
- A Functional Map for Diverse Forelimb Actions within Brainstem Circuitry
- A Recurrent GOF Mutation in CLCN6 Causes Early-Onset Neurodegeneration
- An Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques
- Antidepressant Actions of Ketamine Engage Cell-Specific Translation via eIF4E
- Applications of Machine Learning to Diagnosis and Treatment of Neurodegenerative Diseases
- Association of Klotho-VS Heterozygosity With Risk of AD in Individuals with APOE4
- Association of Symptoms of Depression With Cardiovascular Disease
- Association of Youth Depression With Somatic Diseases and Premature Death
- Astrocytes Phagocytose Adult Hippocampal Synapses for Circuit Homeostasis
- Base Editing Strategy Allows Insertion of the A673T Mutation in APP Gene to Prevent the Development of Alzheimer's Disease
- Bidirectional Perisomatic Inhibitory Plasticity of a Fos Neuronal Network
- Cell Type-Specific Lipid Storage Changes in Parkinson's Disease Patient Brains are Recapitulated by Experimental Glycolipid Disturbance
- Chi3l1/YKL-40 Is Controlled by the Astrocyte Circadian Clock and Regulates Neuroinflammation and Alzheimer's Disease Pathogenesis
- CLR01 Protects Dopaminergic Neurons In Vitro and in Mouse Models of Parkinson's Disease
- Cranial Suture Regeneration and Craniosynostosis
- Cryo-EM Structure of Islet Amyloid Polypeptide Fibrils Reveals Similarities with Amyloid-β Fibrils
- Depression in Individuals who Subsequently Develop Inflammatory Bowel Disease: A Population-Based Nested Case-Control Study
- Diabetes Medications and Risk of Parkinson's Disease: A Cohort Study of Patients with Diabetes
- Differential Attentional Control Mechanisms by Two Distinct Noradrenergic Coeruleo-Frontal Cortical Pathways
- Effects of Acute Sleep Loss on Diurnal Plasma Dynamics of CNS Health Biomarkers in Young Men
- Estrogen Receptor-α Expressing Neurons in the Ventrolateral VMH Regulate Glucose Balance
- Evidence-Based Prevention of Alzheimer's Disease: Systematic Review and Meta-Analysis of 243 Observational Prospective Studies and 153 Randomised Controlled Trials
- Flexible and Stretchable Opto-Electric Neural Interface for Low-Noise Electrocorticogram Recordings and Neuromodulation In Vivo
- Flexible Fiber Probe for Efficient Neural Stimulation and Detection
- Forelimb Movements Evoked by Optogenetic Stimulation of the Macaque Motor Cortex
- G3BPs Tether the TSC Complex to Lysosomes and Suppress mTORC1 Signaling
- GABAergic Signaling to Astrocytes in the Prefrontal Cortex Sustains Goal-Directed Behaviors
- HSP40 Proteins Use Class-Specific Regulation to Drive HSP70 Functional Diversity
- IL-33-PU.1 Transcriptome Reprogramming Drives Functional State Transition
- Increased Dopamine Transmission and Adult Neurogenesis in Trace Amine-Associated Receptor 5 (TAAR5) Knockout Mice
- Landscapes of Bacterial and Metabolic Signatures and Their Interaction in Major Depressive Disorders
- Large-Scale Proteomic Analysis of Alzheimer's Disease Brain and Cerebrospinal Fluid Reveals Early Changes in Energy Metabolism Associated with Microglia and Astrocyte Activation
- M2 Cortex-Dorsolateral Striatum Stimulation Reverses Motor Symptoms and Synaptic Deficits in Huntington's Disease
- Manipulating Synthetic Optogenetic Odors Reveals the Coding Logic of Olfactory Perception
- mGlu2- and mGlu3- Allosteric Modulators Enhance Thalamocortical Transmission
- MIND and Mediterranean Diets Associated with Later Onset of PD
- Mitochondrial Damage-Associated Inflammation Highlights Biomarkers in PRKN/PINK1 Parkinsonism
- Molecular Dissection of Amyloid Disaggregation by Human HSP70
- N-3 Polyunsaturated Fatty Acids Promote Astrocyte Differentiation and Neurotrophin Production Independent of cAMP in Patient-Derived Neural Stem Cells
- Nanozyme Scavenging ROS for Prevention of Pathologic α-Synuclein Transmission in Parkinson's Disease
- Neuroblast Senescence in the Aged Brain Augments Natural Killer Cell Cytotoxicity Leading to Impaired Neurogenesis and Cognition
- NeuroPAL: A Multicolor Atlas for Whole-Brain Neuronal Identification in C. elegans
- Noncanonical Transnitrosylation Network Contributes to Synapse Loss in Alzheimer's Disease
- Patterns of De Novo Tandem Repeat Mutations and Their Role in Autism
- Postnatal Connectomic Development of Inhibition in Mouse Barrel Cortex
- Regulation of Sleep Homeostasis Mediator Adenosine by Basal Forebrain Glutamatergic Neurons
- Restoring Metabolism of Myeloid Cells Reverses Cognitive Decline in Ageing
- Severe Reactive Astrocytes Precipitate Pathological Hallmarks of Alzheimer's Disease via H2O2- Production
- Single-Nucleus Transcriptome Analysis Reveals Dysregulation of Angiogenic Endothelial Cells and Neuroprotective Glia in Alzheimer's Disease
- Small Molecule Cognitive Enhancer Reverses Age-Related Memory Decline in Mice
- STAT3 in the Dorsal Raphe Gates Behavioural Reactivity and Regulates Gene Networks Associated with Psychopathology
- Tau PTM Profiles Identify Patient Heterogeneity and Stages of AD
- The Innate Immunity Protein IFITM3 Modulates γ-Secretase in Alzheimer's Disease
- αS Aggregates Increase the Conductance of Substantia Nigra Dopamine Neurons
- β-Amyloid Clustering around ASC Fibrils Boosts Its Toxicity in Microglia
- A Novel and Accurate Full-Length HTT Mouse Model for Huntington's Disease
- Assessment of Neurovascular Coupling and Cortical Spreading Depression in Mixed Mouse Models of Atherosclerosis and Alzheimer's Disease
- BET1 Variants Establish Impaired Vesicular Transport as a Cause for Muscular Dystrophy with Epilepsy
- Blood-Based Biomarkers for Alzheimer's Disease
- Caldendrin and Myosin V Regulate Synaptic Spine Apparatus Localization via ER Stabilization in Dendritic Spines
- Comparative Study of Brain fMRI of Olfactory Stimulation in NMOSD and MS
- Cysteine String Protein Controls Two Routes of Export for Misfolded Huntingtin
- DSCAM Deficiency Leads to Premature Spine Maturation and Autism-like Behaviors
- Enrichment of SARM1 Alleles Encoding Variants with Constitutively Hyperactive Nadase in Patients with ALS and Other Motor Nerve Disorders
- Genome-Wide Identification of the Genetic Basis of Amyotrophic Lateral Sclerosis
- Human ALS/FTD Brain Organoid Slice Cultures Display Distinct Early Astrocyte and Targetable Neuronal Pathology
- Learning and Attention Increase Visual Response Selectivity through Distinct Mechanisms
- Loss of TREM2 Rescues Hyperactivation of Microglia, But Not Lysosomal Deficits and Neurotoxicity in Models of Progranulin Deficiency
- Macrophages Transfer Mitochondria to Sensory Neurons to Resolve Inflammatory Pain
- Make War Not Love: The Neural Substrate Underlying a State-Dependent Switch in Female Social Behavior
- Microglial PD-1 Stimulation by Astrocytic PD-L1 Suppresses Neuroinflammation and Alzheimer's Disease Pathology
- Mouse Visual Cortex Areas Represent Perceptual and Semantic Features of Learned Visual Categories
- Myelinating Schwann Cells and Netrin-1 Control Intra-Nervous Vascularization of the Developing Mouse Sciatic Nerve
- Neurophysiological and Brain Structural Markers of Cognitive Frailty Differ from AD
- Neurotoxin-Mediated Potent Activation of the Axon Degeneration Regulator SARM1
- Postnatal Expression of the Lysine Methyltransferase SETD1B is Essential for Learning and the Regulation of Neuron-Enriched Genes
- Synaptic Targets of Photoreceptors Specialized to Detect Color and Skylight Polarization in Drosophila
- Serotonergic Neurons Translate Taste Detection into Internal Nutrient Regulation
- Systematic Phenotyping and Characterization of the 3xTg-AD Mouse Model of AD
- The Preference for Sugar Over Sweetener Depends on a Gut Sensor Cell
- The SARS-CoV-2 Main Protease Mpro Causes Microvascular Brain Pathology by Cleaving NEMO in Brain Endothelial Cells
- Trans ε-Viniferin Decreases Amyloid Deposits with Greater Efficiency Than Resveratrol in an Alzheimer's Mouse Model
- Transcriptomic Taxonomy and Neurogenic Trajectories of Adult Human, Macaque, and Pig Hippocampal and Entorhinal Cells
- Nature Aging: Glial Cells Identify and Clear Aβ through the VCAM1-ApoE Pathway and Alleviating Alzheimer's Disease Pathology
- Cell Stem Cell: Transplanting Neurons for Epilepsy Treatment Achieves a New Breakthrough
- Nature Communications: Scientists Identify Unique Circular RNAs in Parkinson's Disease
- Science: New Study Reveals the Mechanism of The Extensive Neuronal Loss in Alzheimer's Disease
- Nature Communications: Scientists Identified a Calcium Ion Channel Linked to Brain Inflammation
- Neuron: New Discovery Subverts Common Understanding of Parkinson's Disease Causation
- Science: Presynaptic Ube3a E3 Ligase Facilitates Synaptic Elimination by Suppressing BMP Signaling
- Nature: Newly Discovered Special Neurons - Glutamatergic Astrocytes
- Brain: Restoring KCC2 in Neurons Holds Promise for Improving Cognitive Performance of Alzheimer's Disease
The SARS-CoV-2 Main Protease Mpro Causes Microvascular Brain Pathology by Cleaving NEMO in Brain Endothelial Cells
Coronavirus disease 2019 (COVID-19) can damage cerebral small vessels and cause neurological symptoms. Here we describe structural changes in cerebral small vessels of patients with COVID-19 and elucidate potential mechanisms underlying the vascular pathology. In brains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals and animal models, we found an increased number of empty basement membrane tubes, so-called string vessels representing remnants of lost capillaries. We obtained evidence that brain endothelial cells are infected and that the main protease of SARS-CoV-2 (Mpro) cleaves NEMO, the essential modulator of nuclear factor-κB. By ablating NEMO, Mpro induces the death of human brain endothelial cells and the occurrence of string vessels in mice. Deletion of receptor-interacting protein kinase (RIPK) 3, a mediator of regulated cell death, blocks the vessel rarefaction and disruption of the blood–brain barrier due to NEMO ablation. Importantly, a pharmacological inhibitor of RIPK signaling prevented the Mpro-induced microvascular pathology. Our data suggest RIPK as a potential therapeutic target to treat the neuropathology of COVID-19.
Reference
Wenzel, J., Lampe, J., Müller-Fielitz, H., Schuster, R., Zille, M., Müller, K., ... & Schwaninger, M. (2021). The SARS-CoV-2 main protease Mpro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells. Nature Neuroscience, 24(11), 1522-1533.