pathway

COMPLEMENT

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about COMPLEMENT: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

3516Connections

30Hypotheses

0Analyses

50Outgoing

50Incoming

20Experiments

0Debates

Summary

COMPLEMENT is a biological pathway involved in neurodegeneration research. Key relationships include: activates, regulates, associated with. Associated with ALS, ALZHEIMER, ALZHEIMER'S. Connected to 1045 entities in the SciDEX knowledge graph.

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🔀 Pathway Info

Name	COMPLEMENT
Key Genes/Proteins	ABCA1, ABI3, ACE, ACETYL-COA, ACSL4, ACTB
Related Diseases	aging, Aging
Related Pathways	Adaptive Immunity

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

Complement Inhibitor Therapy in Neurodegeneration

therapeutic · 2044 words

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Pathway Diagram

graph TD
    COMPLEMENT["COMPLEMENT"] -->|"regulates"| SYNAPSE_ELIMINATION["SYNAPSE_ELIMINATION"]
    COMPLEMENT["COMPLEMENT"] -->|"activates"| Als["Als"]
    COMPLEMENT["COMPLEMENT"] -->|"activates"| Ms["Ms"]
    COMPLEMENT["COMPLEMENT"] -->|"interacts"| Als_1["Als"]
    COMPLEMENT["COMPLEMENT"] -->|"interacts"| Autism["Autism"]
    COMPLEMENT["COMPLEMENT"] -->|"therapeutic target"| Als_2["Als"]
    CEBPB["CEBPB"] -->|"regulates"| COMPLEMENT["COMPLEMENT"]
    NPTX2["NPTX2"] -->|"regulates"| COMPLEMENT["COMPLEMENT"]
    IGF2BP1["IGF2BP1"] -->|"interacts"| COMPLEMENT["COMPLEMENT"]
    ANK2["ANK2"] -->|"interacts"| COMPLEMENT["COMPLEMENT"]
    style COMPLEMENT fill:#1b5e20,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (1447)

Target	Relation	Type	Str
Inflammation	therapeutic_target	disease	1.00
Complement	inhibits	pathway	1.00
Complement	associated_with	pathway	1.00
INFLAMMATION	activates	gene	1.00
Neuroinflammation	activates	disease	1.00
Neurodegeneration	activates	disease	1.00
C1Q	activates	gene	1.00
Alzheimer	activates	disease	1.00
Als	activates	disease	1.00
ASTROCYTES	activates	gene	1.00
Inflammation	activates	disease	1.00
NEUROINFLAMMATION	activates	gene	1.00
Complement	regulates	pathway	1.00
Complement	activates	pathway	1.00
Als	therapeutic_target	disease	1.00
Complement	therapeutic_target	pathway	1.00
ALZHEIMER	activates	gene	1.00
Aging	activates	disease	1.00
MICROGLIA	activates	gene	1.00
h-6b9dec7170	targeted_by	hypothesis	1.00
MICROGLIA	therapeutic_target	gene	1.00
Phagocytosis	activates	pathway	1.00
NEURON	activates	gene	1.00
CYTOKINES	activates	gene	1.00
ALZHEIMER'S DISEASE	activates	gene	1.00
AMYLOID	activates	gene	1.00
Cancer	therapeutic_target	disease	0.95
Synaptic Pruning	mediates	process	0.95
Als	regulates	disease	0.95
Synapse Loss	mediates	phenotype	0.95
Als	associated_with	disease	0.95
NEUROMYELITIS OPTICA SPECTRUM DISORDER	therapeutic_target	entity	0.90
Alzheimer's Disease	involved_in	disease	0.90
Glaucoma	contributes_to	disease	0.90
Oxidative Stress	activates	pathway	0.90
Complement	implicated_in	pathway	0.90
MICROGLIA	regulates	gene	0.90
Complement	contributes_to	pathway	0.90
Immune Response	regulates	pathway	0.90
PHAGOCYTOSIS	activates	gene	0.90
Neurodegeneration	therapeutic_target	disease	0.85
Parkinson	activates	disease	0.85
Alzheimer	inhibits	disease	0.85
Inflammation	regulates	disease	0.85
Infection	activates	disease	0.85
Als	inhibits	disease	0.85
Alzheimer's Disease	associated_with	disease	0.85
Neurodegeneration	mediates	process	0.85
Alzheimer	associated_with	disease	0.85
Alzheimer	therapeutic_target	disease	0.85

Incoming (2069)

Source	Relation	Type	Str
Als	therapeutic_target	disease	1.00
CYTOKINES	activates	gene	1.00
NEURODEGENERATION	activates	gene	1.00
INFLAMMATION	activates	gene	1.00
NEUROINFLAMMATION	activates	gene	1.00
COMPLEMENT	regulates	gene	1.00
COMPLEMENT	inhibits	gene	1.00
Inflammation	therapeutic_target	disease	1.00
ALZHEIMER'S DISEASE	activates	gene	1.00
COMPLEMENT	associated_with	gene	1.00
COMPLEMENT	activates	gene	1.00
Als	regulates	disease	1.00
Inflammation	regulates	disease	1.00
ASTROCYTES	activates	gene	1.00
Neurodegeneration	activates	disease	1.00
h-6b9dec7170	targets	hypothesis	1.00
ALZHEIMER	activates	gene	1.00
INFLAMMATION	therapeutic_target	gene	1.00
COMPLEMENT	therapeutic_target	gene	1.00
AMYLOID	activates	gene	1.00
MICROGLIA	regulates	gene	1.00
Als	activates	disease	1.00
Aging	activates	disease	1.00
MICROGLIA	activates	gene	1.00
C1Q	activates	gene	1.00
Alzheimer	activates	disease	1.00
Neuroinflammation	activates	disease	1.00
Cancer	therapeutic_target	disease	1.00
Inflammation	activates	disease	1.00
CANCER	therapeutic_target	gene	1.00
MICROGLIA	therapeutic_target	gene	1.00
Als	associated_with	disease	1.00
NEURON	activates	gene	1.00
PHAGOCYTOSIS	activates	gene	1.00
NEURODEGENERATION	regulates	gene	1.00
GENES	regulates	gene	1.00
NEURODEGENERATION	activates	gene	1.00
OXIDATIVE STRESS	activates	gene	1.00
INFLAMMATION	regulates	gene	1.00
Als	inhibits	disease	1.00
Early Metastatic Epithelial Cell Clusters	involved_in	cell_type	0.90
Alzheimer	therapeutic_target	disease	0.90
C1Q	inhibits	gene	0.90
GENES	activates	gene	0.90
TAU	activates	gene	0.90
ALZHEIMER'S DISEASE	therapeutic_target	gene	0.90
CANCER	activates	gene	0.90
NEURODEGENERATIVE DISEASES	activates	gene	0.90
NEUROINFLAMMATION	therapeutic_target	gene	0.90
Cancer	activates	disease	0.90

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
SASP-Mediated Complement Cascade Amplification	0.910	neurodegeneration	Senolytic therapy for age-related neurod
Complement Cascade Inhibition Synaptic Protection	0.867	neurodegeneration	View
Senescent Cell ASM-Complement Cascade Intervention	0.852	neurodegeneration	Lipid raft composition changes in synapt
Targeting SASP-Complement Amplification Through HIF-1α Downs	0.793	neurodegeneration	What molecular mechanism causes VCP muta
Selective blockade of classical-pathway activation downstrea	0.750	neurodegeneration	Does C1q function differ based on subcel

Complement-SASP Amplification Cascade as Mechanistic Link	0.741	neurodegeneration	Why have anti-Aβ clinical trials failed
Microglial TREM2-Complement Axis Modulation	0.726	neurodegeneration	Cell type vulnerability in Alzheimer's D
Differential Complement Regulator Expression on Synaptic Mem	0.725	synaptic biology	What determines the selectivity of compl
Excessive C1q/C3/CR3 complement cascade activation initiates	0.720	neurodegeneration	Synaptic pruning by microglia in neurode
Complement C1q Mimetic Decoy Therapy	0.695	neurodegeneration	Synaptic pruning by microglia in early A
Microglia and complement sustain post-Aβ neurodegeneration a	0.690	neurodegeneration	Does tau dendritic missorting persist in
Complement C1QA Spatial Gradient in Cortical Layers	0.678	Alzheimer's Disease	SEA-AD Gene Expression Profiling — Allen
Age-Dependent Complement C4b Upregulation Drives Synaptic Vu	0.671	neurodegeneration	Gene expression changes in aging mouse b
Microglial TREM2 state determines whether C1q-tagged substra	0.670	neurodegeneration	Does C1q function differ based on subcel
LPS-primed microglial trained immunity establishes persisten	0.670	neurodegeneration	Synaptic pruning by microglia in neurode
Complement C1q Subtype Switching	0.665	neurodegeneration	4R-tau strain-specific spreading pattern
Astrocyte IL-1β as Paracrine Mediator of Microglial Compleme	0.660	neuroinflammation	How does sevoflurane-induced NF-κB activ
Complement C1QA Inhibition Synergizes with PV Interneuron Mo	0.659	neurodegeneration	What molecular mechanisms underlie the d
SUMO1-Mediated Synaptotagmin-1 SUMOylation at Lys124 Impairs	0.652	neurodegeneration	What are the specific PTM changes in syn
C1q has spatially distinct functions, with synapse-bound C1q	0.630	neurodegeneration	Does C1q function differ based on subcel
APOE4-microglial complement signaling causes cholinergic-enr	0.630	neurodegeneration	What determines the temporal sequence of
Tau fibrils expose neuronal phosphatidylserine and heat-shoc	0.620	neurodegeneration	Synaptic pruning by microglia in neurode
Complement Cascade Specificity: Microglial C3aR Antagonism D	0.618	synaptic biology	Does SPP1-mediated synaptic engulfment r
Complement-Mediated Synaptic Pruning Dysregulation	0.612	neurodegeneration	Gene expression changes in aging mouse b
H2: Perforant Path Synapse Loss via Early Complement Cascade	0.610	neurodegeneration	Entorhinal cortex layer II vulnerability
Female microglia exhibit heightened complement gene expressi	0.610	neurodegeneration	Synaptic pruning by microglia in neurode
TNF-α–C1r/C1s Bridge Between NF-κB and Classical Complement	0.600	neuroinflammation	How does sevoflurane-induced NF-κB activ
NAMPT-SIRT1 Axis as Master Regulator of SASP-Dependent Compl	0.592	neurodegeneration	test
TREM2-C1Q Competitive Binding to Prevent Complement-Mediated	0.591	neurodegeneration	Do β-amyloid plaques and neurofibrillary
H5: Complement Dysregulation Drives Synapse Loss via Senesce	0.580	neurodegeneration	Do APOE4-driven senescent astrocytes cau

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (20)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Single-cell RNA sequencing analysis of human atherosclerotic plaques	exploratory	Atherosclerosis	0.900	0.00	Human atherosclerotic plaque s	proposed	N/A
C1q neutralization experiment	validation	perioperative neurocognitive d	0.900	0.00	rats	proposed	N/A
scRNA-seq analysis of human atherosclerotic plaques	exploratory	Atherosclerosis	0.900	0.00	human atherosclerotic plaque s	proposed	N/A
Sevoflurane-induced neurotoxicity (SIN) model in rats	validation	perioperative neurocognitive d	0.900	0.00	rats	proposed	N/A
Machine learning-based identification of C1Q hub genes	exploratory	Atherosclerosis	0.900	0.00	Human bulk RNA sequencing data	proposed	N/A
Gene expression validation in apoE-/- mice	validation	Atherosclerosis	0.850	0.00	apoE-/- mice	proposed	N/A
ox-LDL treatment of RAW264.7 macrophages	exploratory	Atherosclerosis	0.850	0.00	RAW264.7 macrophages	proposed	N/A
Validation of hub genes in ox-LDL treated RAW264.7 macrophages	exploratory	Atherosclerosis	0.800	0.00	RAW264.7 macrophages	proposed	N/A
Validation of hub genes in apoE-/- atherosclerotic mice	validation	Atherosclerosis	0.800	0.00	apoE-/- mice	proposed	N/A
Proposed experiment from debate on Synaptic pruning by microglia in ea	falsification	Alzheimer's Disease	0.400	0.50	mouse	proposed	$200,000
Proposed experiment from debate on Senolytics targeting p16/p21+ senes	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000
Biomechanical Impact Profiles and Chronic Traumatic Encephalopathy Phe	clinical	Neurodegeneration	0.400	0.50	in_silico	proposed	$180,000
Mechanism: Why Does Amyloid Removal Only Slow Decline 27%?	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$7,500,000
Experiment: Autoimmune Hypothesis Testing in AD	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
Experimental: CAAR-T Cell Therapy for Autoantibody-Mediated Neurotoxic	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
cGAS-STING Pathway Validation Study in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$7,100,000
Microglial Aging and Immune Memory in Neurodegeneration — Training the	validation	Alzheimer's Disease	0.400	0.50	human	proposed	$2,960,000
Microglial Contributions to Huntington's Disease Pathogenesis	validation	Neuroinflammation	0.400	0.50	human	proposed	$2,960,000
Mixed Pathology Effects on Parkinson's Disease Progression and Treatme	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
s:** - Compare brain penetration in FcRn+/+ vs FcRn-/- mice with engin	falsification	Neuroinflammation	0.400	0.50	mouse	proposed	$200,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Prolonged anesthesia induces neuroinflammation and complement-mediated microglia [PMID:36600274]	Xu F, Han L, Wang Y, Deng D, Ding Y, Zha	BMC Med	2023	2
Perivascular cells induce microglial phagocytic states and synaptic engulfment v [PMID:36747024]	De Schepper S, Ge JZ, Sierksma A, Crowle	Nat Neurosci	2023	2
An integrative analysis of single-cell and bulk transcriptome and bidirectional [PMID:38179058]	Cui HK, Tang CJ, Gao Y, Li ZA, Zhang J,	Front Immunol	2023	2
Complement, Inflammasome, and Microglial Crosstalk in Glaucoma: From Neurodegene [PMID:41900887]	Chen TY, Wu N, Sun X	Life (Basel)	2026	1
Systemic Neurodegeneration and Brain Aging: Multi-Omics Disintegration, Proteost [PMID:40868276]	Voicu V, Toader C, Șerban M, Covache-Bus	Biomedicines	2025	1
Complement C1q/C3-CR3 signaling pathway mediates abnormal microglial phagocytosi [PMID:38642614]	Han QQ, Shen SY, Liang LF, Chen XR, Yu J	Brain Behav Immun	2024	1
Metabolic orchestration of cell death by AMPK-mediated phosphorylation of RIPK1. [PMID:37384704]	Zhang T, Xu D, Trefts E, Lv M, Inuzuka H	Science	2023	1
Microglia regulation of synaptic plasticity and learning and memory. [PMID:34472455]	Cornell J, Salinas S, Huang HY, Zhou M	Neural Regen Res	2022	1
Early complement genes are associated with visual system degeneration in multipl [PMID:31289819]	Fitzgerald KC, Kim K, Smith MD, Aston SA	Brain	2019	1
Complement and microglia mediate early synapse loss in Alzheimer mouse models. [PMID:27033548]	Hong S, Beja-Glasser VF, Nfonoyim BM, Fr	Science	2016	1
Panacis Quinquefolii Radix Polysaccharides Alleviate Depressive-Like Behaviors i [PMID:41914021]	Xie M, Feng L, Li R, Li M, Shen L, Zhang	CNS neuroscience & therapeutic	2026	0
Vaccine-induced antibodies can limit Salmonella infection in the absence of comp [PMID:41738756]	Perez-Toledo M, Aksu-Istil K, Marcial-Ju	mBio	2026	0
The gain-of-function TREM2-T96K mutation increases risk for Alzheimer's disease [PMID:41109213]	Pilat DJ, Le H, Prokopenko D, Lin CJ, Ei	Neuron	2026	0
The Immuno-Glial Connectome in Alzheimer's Disease: Integrating Central and Peri [PMID:41569436]	Gopalakrishna PK, Che Mohd Nassir CMN, A	Cellular and molecular neurobi	2026	0
Phosphoproteomics uncovers a neuroimmune perspective on trigeminal neuralgia: se [PMID:41853292]	Zhai X, Lin X, Zhang L, Ren Y, Miao H, M	Frontiers in immunology	2026	0
Messengers of coagulopathy: complement-carrying extracellular vesicles in SARS-C [PMID:41766448]	Taxiarchis A, Pruner I	Current opinion in hematology	2026	0
Alzheimer's Disease as a Disorder of Neuroimmune Dysregulation. [PMID:41745721]	Aranda-Abreu GE, Rojas-Durán F, Hernánde	Neurology international	2026	0
Proteomic Signature in Men with Central Serous Chorioretinopathy. [PMID:41641862]	Chambon C, Picard E, Zola M, Aichedo S,	Journal of proteome research	2026	0
Machine Learning and Blood-Targeted Proteomics Enable Early Prediction and Etiol [PMID:41683823]	Starodubtseva N, Tokareva A, Kononikhin	International journal of molec	2026	0
Club cell RhoA activation amplifies allergic airway inflammation by regulating e [PMID:41633491]	Tu W, Wu M, Wan R, Alphonse M, Gu W, Gho	The Journal of allergy and cli	2026	0

Debates (0)

Multi-agent debates referencing this entity

No debates reference this entity