The complement cascade in the regulation of neuroinflammation, nociceptive sensitization, and pain

Fully defined human pluripotent stem cell-derived microglia and tri-culture system model C3 production in Alzheimer’s disease

(2021) Sudha R. Guttikonda et al.   NATURE NEUROSCIENCE

Avacopan for the Treatment of ANCA-Associated Vasculitis

(2021) David R.W. Jayne et al.   NEW ENGLAND JOURNAL OF MEDICINE

Human cells and networks of pain: Transforming pain target identification and therapeutic development

(2021) William Renthal et al.   NEURON

Emerging Role of C5 Complement Pathway in Peripheral Neuropathies: Current Treatments and Future Perspectives

(2021) Cristina Giorgio et al.   Biomedicines

First approval of a complement C3 inhibitor opens up autoimmune and inflammatory opportunities

(2021) Asher Mullard   NATURE REVIEWS DRUG DISCOVERY

Complement-Mediated Events in Alzheimer’s Disease: Mechanisms and Potential Therapeutic Targets

(2020) Andrea J. Tenner   JOURNAL OF IMMUNOLOGY

The VGF-derived peptide TLQP21 impairs purinergic control of chemotaxis and phagocytosis in mouse microglia

(2020) Nirmeen Elmadany et al.   JOURNAL OF NEUROSCIENCE

Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain

(2020) Xiaobing Yu et al.   Nature Communications

Preclinical Pharmacokinetics of Complement C5a Receptor Antagonists PMX53 and PMX205 in Mice

(2020) Vinod Kumar et al.   ACS Omega

Complement Membrane Attack Complex

(2020) Catherine B. Xie et al.   AMERICAN JOURNAL OF PATHOLOGY

Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease

(2020) Wei-Ting Chen et al.   CELL

C5aR2 Activation Broadly Modulates the Signaling and Function of Primary Human Macrophages

(2020) Xaria X. Li et al.   JOURNAL OF IMMUNOLOGY

Absence of the C5a Receptor C5aR2 Worsens Ischemic Tissue Injury by Increasing C5aR1-Mediated Neutrophil Infiltration

(2020) Mike C. L. Wu et al.   JOURNAL OF IMMUNOLOGY

Transcriptional Reprogramming of Distinct Peripheral Sensory Neuron Subtypes after Axonal Injury

(2020) William Renthal et al.   NEURON

Overexpression of schizophrenia susceptibility factor human complement C4A promotes excessive synaptic loss and behavioral changes in mice

(2020) Melis Yilmaz et al.   NATURE NEUROSCIENCE

C5a complement and cytokine signaling mediate the pronociceptive effects of complex regional pain syndrome patient IgM in fracture mice

(2020) Xiaoyou Shi et al.   PAIN

Complement targets newborn retinal ganglion cells for phagocytic elimination by microglia

(2019) Sarah R Anderson et al.   JOURNAL OF NEUROSCIENCE

Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning

(2019) Carl M. Sellgren et al.   NATURE NEUROSCIENCE

Eculizumab in paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome: 10-year pharmacovigilance analysis

(2019) Gérard Socié et al.   BRITISH JOURNAL OF HAEMATOLOGY

Clinical promise of next-generation complement therapeutics

(2019) Dimitrios C. Mastellos et al.   NATURE REVIEWS DRUG DISCOVERY

Microglia Are Indispensable for Synaptic Plasticity in the Spinal Dorsal Horn and Chronic Pain

(2019) Li-Jun Zhou et al.   Cell Reports

Beyond the Ligand: Extracellular and Transcellular G Protein–Coupled Receptor Complexes in Physiology and Pharmacology

(2019) Henry A. Dunn et al.   PHARMACOLOGICAL REVIEWS

Complement dysregulation in the central nervous system during development and disease

(2019) John D. Lee et al.   SEMINARS IN IMMUNOLOGY

Neuronal complement cascade drives bone cancer pain via C3R mediated microglial activation

(2018) Xiaoxia Huang et al.   BRAIN RESEARCH

Role of Complement in a Rat Model of Paclitaxel-Induced Peripheral Neuropathy

(2018) Jijun Xu et al.   JOURNAL OF IMMUNOLOGY

Complement components are upregulated and correlate with disease progression in the TDP-43Q331K mouse model of amyotrophic lateral sclerosis

(2018) John D. Lee et al.   Journal of Neuroinflammation

New tricks for an ancient system: Physiological and pathological roles of complement in the CNS

(2018) Andrea J. Tenner et al.   MOLECULAR IMMUNOLOGY

Microglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential

(2018) Kazuhide Inoue et al.   NATURE REVIEWS NEUROSCIENCE

Complement: The Emerging Architect of the Developing Brain

(2018) Liam G. Coulthard et al.   TRENDS IN NEUROSCIENCES

Macrophage angiotensin II type 2 receptor triggers neuropathic pain

(2018) Andrew J. Shepherd et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Changes in the Synaptic Proteome in Tauopathy and Rescue of Tau-Induced Synapse Loss by C1q Antibodies

(2018) Borislav Dejanovic et al.   NEURON

Complement C3aR Inactivation Attenuates Tau Pathology and Reverses an Immune Network Deregulated in Tauopathy Models and Alzheimer’s Disease

(2018) Alexandra Litvinchuk et al.   NEURON

Mechanisms underlying mechanical sensitization induced by complement C5a

(2018) Charles A. Warwick et al.   PAIN

Complement 3a receptor in dorsal horn microglia mediates pronociceptive neuropeptide signaling

(2017) Suzanne Doolen et al.   GLIA

Monitoring C5aR2 Expression Using a Floxed tdTomato-C5aR2 Knock-In Mouse

(2017) Christian M. Karsten et al.   JOURNAL OF IMMUNOLOGY

Monitoring C3aR Expression Using a Floxed tdTomato-C3aR Reporter Knock-in Mouse

(2017) Katharina M. Quell et al.   JOURNAL OF IMMUNOLOGY

The Alternative Receptor for Complement Component 5a, C5aR2, Conveys Neuroprotection in Traumatic Spinal Cord Injury

(2017) Patrick J.C. Biggins et al.   JOURNAL OF NEUROTRAUMA

Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis

(2017) David R.W. Jayne et al.   JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY

C1q: A fresh look upon an old molecule

(2017) Nicole M. Thielens et al.   MOLECULAR IMMUNOLOGY

Structural plasticity and reorganisation in chronic pain

(2017) Rohini Kuner et al.   NATURE REVIEWS NEUROSCIENCE

Complement C3 deficiency protects against neurodegeneration in aged plaque-rich APP/PS1 mice

(2017) Qiaoqiao Shi et al.   Science Translational Medicine

Complement in the pathogenesis of Alzheimer’s disease

(2017) B. Paul Morgan   Seminars in Immunopathology

Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss

(2017) Sheri L. Peterson et al.   Scientific Reports

Complement peptide C3a stimulates neural plasticity after experimental brain ischaemia

(2016) Anna Stokowska et al.   BRAIN

Spinal versus brain microglial and macrophage activation traits determine the differential neuroinflammatory responses and analgesic effect of minocycline in chronic neuropathic pain

(2016) Zhilin Li et al.   BRAIN BEHAVIOR AND IMMUNITY

Complement-Mediated Regulation of Metabolism and Basic Cellular Processes

(2016) Christoph Hess et al.   IMMUNITY

Complement activation at the motor end-plates in amyotrophic lateral sclerosis

(2016) Nawal Bahia El Idrissi et al.   Journal of Neuroinflammation

The Complement System Component C5a Produces Thermal Hyperalgesia via Macrophage-to-Nociceptor Signaling That Requires NGF and TRPV1

(2016) Leonid P. Shutov et al.   JOURNAL OF NEUROSCIENCE

TNF-α Differentially Regulates Synaptic Plasticity in the Hippocampus and Spinal Cord by Microglia-Dependent Mechanisms after Peripheral Nerve Injury

(2016) Yong Liu et al.   JOURNAL OF NEUROSCIENCE

Astrocyte-Microglia Cross Talk through Complement Activation Modulates Amyloid Pathology in Mouse Models of Alzheimer's Disease

(2016) H. Lian et al.   JOURNAL OF NEUROSCIENCE

Schizophrenia risk from complex variation of complement component 4

(2016) Aswin Sekar et al.   NATURE

Surgical extraction of human dorsal root ganglia from organ donors and preparation of primary sensory neuron cultures

(2016) Manouela V Valtcheva et al.   Nature Protocols

Expression of C1ql3 in Discrete Neuronal Populations Controls Efferent Synapse Numbers and Diverse Behaviors

(2016) David C. Martinelli et al.   NEURON

C5a and pain development: An old molecule, a new target

(2016) Andreza U. Quadros et al.   PHARMACOLOGICAL RESEARCH

Complement and microglia mediate early synapse loss in Alzheimer mouse models

(2016) S. Hong et al.   SCIENCE

Inhibition of Complement Retards Ankylosing Spondylitis Progression

(2016) Chaoqun Yang et al.   Scientific Reports

Complement activation, regulation, and molecular basis for complement-related diseases

(2015) G. Bajic et al.   EMBO JOURNAL

Monitoring and Cell-Specific Deletion of C5aR1 Using a Novel Floxed GFP-C5aR1 Reporter Knock-in Mouse

(2015) Christian M. Karsten et al.   JOURNAL OF IMMUNOLOGY

C4a: An Anaphylatoxin in Name Only

(2015) Scott R. Barnum   Journal of Innate Immunity

Persistent Nociception Triggered by Nerve Growth Factor (NGF) Is Mediated by TRPV1 and Oxidative Mechanisms

(2015) M. A. Eskander et al.   JOURNAL OF NEUROSCIENCE

Complement Protein C1q Modulates Neurite Outgrowth In Vitro and Spinal Cord Axon Regeneration In Vivo

(2015) S. L. Peterson et al.   JOURNAL OF NEUROSCIENCE

The Complement Receptor C5aR Controls Acute Inflammation and Astrogliosis following Spinal Cord Injury

(2015) F. H. Brennan et al.   JOURNAL OF NEUROSCIENCE

The role of heparan sulfate as determining pathogenic factor in complement factor H-associated diseases

(2015) Markus A. Loeven et al.   MOLECULAR IMMUNOLOGY

Complement, a target for therapy in inflammatory and degenerative diseases

(2015) B. Paul Morgan et al.   NATURE REVIEWS DRUG DISCOVERY

Anterograde C1ql1 Signaling Is Required in Order to Determine and Maintain a Single-Winner Climbing Fiber in the Mouse Cerebellum

(2015) Wataru Kakegawa et al.   NEURON

Complementing the Sugar Code: Role of GAGs and Sialic Acid in Complement Regulation

(2015) Alex Langford-Smith et al.   Frontiers in Immunology

Complement and Its Receptors: New Insights into Human Disease

(2014) V. Michael Holers   Annual Review of Immunology

The Complement Factor C5a Contributes to Pathology in a Rat Model of Amyotrophic Lateral Sclerosis

(2014) T. M. Woodruff et al.   JOURNAL OF IMMUNOLOGY

A New Map of Glycosaminoglycan and C3b Binding Sites on Factor H

(2014) C. Q. Schmidt et al.   JOURNAL OF IMMUNOLOGY

Elevation of the terminal complement activation products C5a and C5b-9 in ALS patient blood

(2014) S. Mantovani et al.   JOURNAL OF NEUROIMMUNOLOGY

Complement Nomenclature 2014

(2014) Claudia Kemper et al.   MOLECULAR IMMUNOLOGY

Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing

(2014) Dmitry Usoskin et al.   NATURE NEUROSCIENCE

The VGF-derived peptide TLQP-21 contributes to inflammatory and nerve injury-induced hypersensitivity

(2014) Carolyn A. Fairbanks et al.   PAIN

Autoimmunity contributes to nociceptive sensitization in a mouse model of complex regional pain syndrome

(2014) Wen-Wu Li et al.   PAIN

Comparison of pain outcomes between two anti-GD2 antibodies in patients with neuroblastoma

(2014) Doralina L. Anghelescu et al.   PEDIATRIC BLOOD & CANCER

Role for terminal complement activation in amyotrophic lateral sclerosis disease progression

(2014) T. M. Woodruff et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Targeting the minor pocket of C5aR for the rational design of an oral allosteric inhibitor for inflammatory and neuropathic pain relief

(2014) Alessio Moriconi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structural and functional characterization of human and murine C5a anaphylatoxins

(2014) Janus Asbjørn Schatz-Jakobsen et al.   ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

Molecular Interactions between Complement Factor H and Its Heparin and Heparan Sulfate Ligands

(2014) Stephen J. Perkins et al.   Frontiers in Immunology

Alloantibody and Complement Promote T Cell–Mediated Cardiac Allograft Vasculopathy Through Noncanonical Nuclear Factor-κB Signaling in Endothelial Cells

(2013) Dan Jane-wit et al.   CIRCULATION

Abnormal activation of complement C3 in the spinal dorsal horn is closely associated with progression of neuropathic pain

(2013) FACHUAN NIE et al.   INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE

Tissue-Specific Host Recognition by Complement Factor H Is Mediated by Differential Activities of Its Glycosaminoglycan-Binding Regions

(2013) S. J. Clark et al.   JOURNAL OF IMMUNOLOGY

Complement in Immune and Inflammatory Disorders: Pathophysiological Mechanisms

(2013) D. Ricklin et al.   JOURNAL OF IMMUNOLOGY

Dysregulation of the complement cascade in the hSOD1G93A transgenic mouse model of amyotrophic lateral sclerosis

(2013) John D Lee et al.   Journal of Neuroinflammation

Nuclear Calcium Signaling in Spinal Neurons Drives a Genomic Program Required for Persistent Inflammatory Pain

(2013) Manuela Simonetti et al.   NEURON

Cardioembolic and Small Vessel Disease Stroke Show Differences in Associations between Systemic C3 Levels and Outcome

(2013) Anna Stokowska et al.   PLoS One

Roles of Gr-1+ Leukocytes in Postincisional Nociceptive Sensitization and Inflammation

(2012) Peyman Sahbaie et al.   ANESTHESIOLOGY

The Complement System: An Unexpected Role in Synaptic Pruning During Development and Disease

(2012) Alexander H. Stephan et al.   Annual Review of Neuroscience

Generation of complement component C5a by ischemic neurons promotes neuronal apoptosis

(2012) Dale Pavlovski et al.   FASEB JOURNAL

Paroxysmal nocturnal hemoglobinuria and other complement-mediated hematological disorders

(2012) Antonio M. Risitano   IMMUNOBIOLOGY

C5aR Expression in a Novel GFP Reporter Gene Knockin Mouse: Implications for the Mechanism of Action of C5aR Signaling in T Cell Immunity

(2012) J. Dunkelberger et al.   JOURNAL OF IMMUNOLOGY

Complement activation in the injured central nervous system: another dual-edged sword?

(2012) Faith H Brennan et al.   Journal of Neuroinflammation

Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner

(2012) Dorothy P. Schafer et al.   NEURON

Plasma Levels of Complement 4a Protein are Increased in Alzheimerʼs Disease

(2011) Stuart Bennett et al.   ALZHEIMER DISEASE & ASSOCIATED DISORDERS

Antagonism of Nerve Growth Factor-TrkA Signaling and the Relief of Pain

(2011) Patrick W. Mantyh et al.   ANESTHESIOLOGY

Increased local concentration of complement C5a contributes to incisional pain in mice

(2011) Jun H Jang et al.   Journal of Neuroinflammation

Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury

(2011) Andrew D Gaudet et al.   Journal of Neuroinflammation

Restriction of Transient Receptor Potential Vanilloid-1 to the Peptidergic Subset of Primary Afferent Neurons Follows Its Developmental Downregulation in Nonpeptidergic Neurons

(2011) D. J. Cavanaugh et al.   JOURNAL OF NEUROSCIENCE

Complement Protein C1q-Mediated Neuroprotection Is Correlated with Regulation of Neuronal Gene and MicroRNA Expression

(2011) M. E. Benoit et al.   JOURNAL OF NEUROSCIENCE

Identification of a central role for complement in osteoarthritis

(2011) Qian Wang et al.   NATURE MEDICINE

Innate and adaptive immunity in amyotrophic lateral sclerosis: Evidence of complement activation

(2011) M. Sta et al.   NEUROBIOLOGY OF DISEASE

Patterns of pain: Meta-analysis of microarray studies of pain

(2011) Michael L. LaCroix-Fralish et al.   PAIN

The complement component C5a receptor mediates pain and inflammation in a postsurgical pain model

(2011) De-Yong Liang et al.   PAIN

The Alternative and Terminal Pathways of Complement Mediate Post-Traumatic Spinal Cord Inflammation and Injury

(2010) Fei Qiao et al.   AMERICAN JOURNAL OF PATHOLOGY

Sodium Channels in Normal and Pathological Pain

(2010) Sulayman D. Dib-Hajj et al.   Annual Review of Neuroscience

Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment

(2010) Kevin D. Beck et al.   BRAIN

Membrane attack complex inhibitor CD59a protects against focal cerebral ischemia in mice

(2010) Denise Harhausen et al.   Journal of Neuroinflammation

Complement: a key system for immune surveillance and homeostasis

(2010) Daniel Ricklin et al.   NATURE IMMUNOLOGY

The effect of botulinum neurotoxin A on sciatic nerve injury-induced neuroimmunological changes in rat dorsal root ganglia and spinal cord

(2010) J. Mika et al.   NEUROSCIENCE

Anti-GD2 with an FC point mutation reduces complement fixation and decreases antibody-induced allodynia

(2010) Linda S. Sorkin et al.   PAIN

Enhanced synaptic connectivity and epilepsy in C1q knockout mice

(2010) Yunxiang Chu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Complement and its role in innate and adaptive immune responses

(2009) Jason R Dunkelberger et al.   CELL RESEARCH

Differential activation of spinal microglial and astroglial cells in a mouse model of peripheral neuropathic pain

(2009) Joanna Mika et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

The complement factor C5a receptor is upregulated in NFL−/− mouse motor neurons

(2009) Saima Humayun et al.   JOURNAL OF NEUROIMMUNOLOGY

Therapeutic potential of complement modulation

(2009) Eric Wagner et al.   NATURE REVIEWS DRUG DISCOVERY

Minocycline reduces the injury-induced expression of prodynorphin and pronociceptin in the dorsal root ganglion in a rat model of neuropathic pain

(2009) J. Mika et al.   NEUROSCIENCE

Nociceptive sensitization by complement C5a and C3a in mouse

(2009) Jun Ho Jang et al.   PAIN

In SituDeposition of Complement in Human Acute Brain Ischaemia

(2009) E. D. Pedersen et al.   SCANDINAVIAN JOURNAL OF IMMUNOLOGY

Complement activation and inhibition: a delicate balance

(2009) A.P. Sjöberg et al.   TRENDS IN IMMUNOLOGY

Strong complement activation after acute ischemic stroke is associated with unfavorable outcomes

(2008) Gábor Széplaki et al.   ATHEROSCLEROSIS

New therapies for hereditary angioedema: Disease outlook changes dramatically

(2008) Michael M. Frank et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

The alternative complement pathway revisited

(2008) Morten Harboe et al.   JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

Complement C3 Deficiency Leads to Accelerated Amyloid   Plaque Deposition and Neurodegeneration and Modulation of the Microglia/Macrophage Phenotype in Amyloid Precursor Protein Transgenic Mice

(2008) M. Maier et al.   JOURNAL OF NEUROSCIENCE

Nociceptors Are Interleukin-1  Sensors

(2008) A. M. Binshtok et al.   JOURNAL OF NEUROSCIENCE

Role of complement C5a in mechanical inflammatory hypernociception: potential use of C5a receptor antagonists to control inflammatory pain

(2007) E Ting et al.   BRITISH JOURNAL OF PHARMACOLOGY

Apoptosis: controlled demolition at the cellular level

(2007) Rebecca C. Taylor et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Complement activation in the peripheral nervous system following the spinal nerve ligation model of neuropathic pain☆

(2007) Margaret E. Levin et al.   PAIN