pathway

complement cascade

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about complement cascade: 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.

271Connections

12Hypotheses

10Analyses

50Outgoing

50Incoming

11Experiments

12Debates

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🔀 Pathway Info

Name	complement cascade
Key Genes/Proteins	ACOX1, ADIPOQ, ADORA2A, AIF1, ALS, AMPK
Related Diseases	Alzheimer's disease
Linked Hypotheses	17 hypotheses

Pathway Diagram

graph TD
    complement_cascade["complement cascade"] -->|"mediates"| GRANULOCYTE_INFILTRATION["GRANULOCYTE INFILTRATION"]
    style GRANULOCYTE_INFILTRATION fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#fff
    complement_cascade["complement cascade"] -->|"causes"| ASTROCYTE["ASTROCYTE"]
    style ASTROCYTE fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#fff
    complement_cascade["complement cascade"] -->|"causes"| OLIGODENDROCYTE["OLIGODENDROCYTE"]
    style OLIGODENDROCYTE fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#fff
    complement_cascade["complement cascade"] -->|"active in"| microglia["microglia"]
    style microglia fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#fff
    complement_cascade["complement cascade"] -->|"active in"| astrocytes["astrocytes"]
    style astrocytes fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#fff
    complement_cascade["complement cascade"] -->|"active in"| oligodendrocytes["oligodendrocytes"]
    style oligodendrocytes fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#fff
    complement_cascade["complement cascade"] -->|"active in"| neurons["neurons"]
    style neurons fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#fff
    AQP4["AQP4"] -->|"activates"| complement_cascade["complement cascade"]
    style AQP4 fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#fff
    Alzheimer_s_disease["Alzheimer's disease"] -->|"involves"| complement_cascade["complement cascade"]
    style Alzheimer_s_disease fill:#1a2a3a,stroke:#ef5350,stroke-width:1px,color:#fff
    C3["C3"] -->|"participates in"| complement_cascade["complement cascade"]
    style C3 fill:#1a2a3a,stroke:#ce93d8,stroke-width:1px,color:#fff
    neurodegeneration["neurodegeneration"] -->|"involves"| complement_cascade["complement cascade"]
    style neurodegeneration fill:#1a2a3a,stroke:#ef5350,stroke-width:1px,color:#fff
    multiple_sclerosis["multiple sclerosis"] -->|"involves"| complement_cascade["complement cascade"]
    style multiple_sclerosis fill:#1a2a3a,stroke:#ef5350,stroke-width:1px,color:#fff
    style complement_cascade fill:#1b5e20,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0,font-weight:bold

Outgoing (78)

Target	Relation	Type	Str
microglial phagocytosis	mediates	process	0.90
synaptic pruning	causes	process	0.90
ASTROCYTE	causes	entity	0.90
OLIGODENDROCYTE	causes	entity	0.90
GRANULOCYTE INFILTRATION	mediates	entity	0.90
neural stem cells	active_in	cell_type	0.90
microglia	active_in	cell_type	0.90
demyelination	mediates	process	0.85
endothelial cells	active_in	cell_type	0.80
hippocampus	modulates	brain_region	0.80
phagocytosis	mediates	process	0.80
Neuromyelitis Optica	causes	disease	0.80
neurons	active_in	cell_type	0.80
unfolded protein response	crosstalk_with	pathway	0.80
astrocytes	active_in	cell_type	0.80
oligodendrocytes	active_in	cell_type	0.80
INFLAMMATION	inhibits	phenotype	0.70
synaptic loss	causes	phenotype	0.70
AGING	stabilizes	phenotype	0.70
MICROGLIA	causes	cell_type	0.70
cortex	active_in	brain_region	0.70
synaptic plasticity	crosstalk_with	pathway	0.70
ASTROCYTE REACTIVITY	inhibits	phenotype	0.70
MICROGLIA	degrades	cell_type	0.70
oxidative stress response	crosstalk_with	pathway	0.60
TAU	associated_with	protein	0.60
macrophages	active_in	cell_type	0.60
hippocampus	active_in	brain_region	0.60
striatum	active_in	brain_region	0.60
synaptic pruning	mediates	process	0.60
interneurons	active_in	cell_type	0.60
T cells	active_in	cell_type	0.60
spinal cord	active_in	brain_region	0.60
blood-brain barrier	active_in	brain_region	0.60
pyroptosis	crosstalk_with	pathway	0.60
MITOPHAGY	associated_with	phenotype	0.50
TNF	associated_with	gene	0.50
CLU	associated_with	gene	0.50
APP	associated_with	gene	0.50
GFAP	associated_with	gene	0.50
ACSL4	associated_with	gene	0.50
APOE	associated_with	gene	0.50
GPX4	associated_with	gene	0.50
ITGAM	associated_with	gene	0.50
PARKIN	associated_with	gene	0.50
PINK1	associated_with	gene	0.50
MTOR	associated_with	gene	0.50
TFEB	associated_with	gene	0.50
LDLR	associated_with	gene	0.50
CSF	associated_with	phenotype	0.50

Incoming (193)

Source	Relation	Type	Str
C3	involved_in	gene	0.95
AQP4	activates	entity	0.95
Alzheimer's disease	involves	disease	0.90
AQP4-antibody	activates	protein	0.90
C1QA	activates	protein	0.90
C1Q	activates	protein	0.90
eculizumab	inhibits	drug	0.90
neurodegeneration	involves	disease	0.90
C1QC	activates	protein	0.90
C1QB	activates	protein	0.90
C1QA	activates	protein	0.90
C3	participates_in	gene	0.90
astrocytes	active_in	cell_type	0.85
DAM microglia	active_in	cell_type	0.85
GFAP	participates_in	gene	0.85
AQP4	activates	protein	0.85
microglia	active_in	cell_type	0.85
C4	participates_in	gene	0.85
neuroinflammation	involves	disease	0.80
multiple sclerosis	involves	disease	0.80
CR3	participates_in	gene	0.80
C1Q	initiates	gene	0.80
APOE	participates_in	gene	0.75
ALS	protects_against	disease	0.70
AQP4	participates_in	gene	0.70
C1QB	participates_in	gene	0.70
C1QA	participates_in	gene	0.70
CD47	participates_in	gene	0.70
TREM2	participates_in	gene	0.70
TYROBP	regulates	gene	0.70
C1q	activates	protein	0.70
PHAGOCYTOSIS	inhibits	phenotype	0.70
ALS	regulates	disease	0.70
cystatin C	modulates	protein	0.70
IL-1β	activates	protein	0.70
TNF	inhibits	gene	0.70
Aβ oligomers	activates	protein	0.70
PHAGOCYTOSIS	protects_against	phenotype	0.70
neurons	active_in	cell_type	0.65
ASTROCYTES	causes	cell_type	0.65
TET2	participates_in	gene	0.65
TREM2	inhibits	gene	0.65
TNF	participates_in	gene	0.65
PLIN3	participates_in	gene	0.60
C5	participates_in	gene	0.60
C1Q	participates_in	gene	0.60
CD4	participates_in	gene	0.60
TFEB	participates_in	gene	0.60
ULK1	participates_in	gene	0.60
C1QC	participates_in	gene	0.60

Targeting Hypotheses (12)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Complement Cascade Inhibition Synaptic Protection	0.867	neurodegeneration	Does the cancer-cystatin-C-TREM2 pathway
Senescent Cell ASM-Complement Cascade Intervention	0.852	neurodegeneration	Lipid raft composition changes in synapt
SASP-Mediated Complement Cascade Amplification	0.822	neurodegeneration	Senolytic therapy for age-related neurod
Excessive C1q/C3/CR3 complement cascade activation initiates	0.720	neurodegeneration	Synaptic pruning by microglia in neurode
Complement Cascade Specificity: Microglial C3aR Antagonism D	0.618	synaptic-biology	Does SPP1-mediated synaptic engulfment r

H2: Perforant Path Synapse Loss via Early Complement Cascade	0.610	neurodegeneration	Entorhinal cortex layer II vulnerability
TNF-α–C1r/C1s Bridge Between NF-κB and Classical Complement	0.600	neuroinflammation	How does sevoflurane-induced NF-κB activ
Timed Senolytic Therapy Eliminates p16^Ink4a/p21^Cip1-Senesc	0.564	neuroinflammation	What molecular mechanisms drive the tran
Combined NAMPT-Alectinib Targeting of SASP-Complement Cascad	0.549	neuroinflammation	How does Alectinib, a kinase inhibitor,
Complement Cascade as Final Common Effector	0.455	neuroinflammation	Why do clinical manifestations overlap d
Complement Cascade Activation Bridges Microglial OxPC Sensin	0.419	neuroinflammation	What molecular mechanisms enable microgl
Astrocyte-Mediated Synaptic Pruning to Optimize Functional C	0.354	connectomics	Human connectome alterations in Alzheime

Mentioning Analyses (10)

Scientific analyses that reference this entity

Test Preregistration Analysis

neurodegeneration | 2026-04-27 | 7 hypotheses Top: 0.710

Does the cancer-cystatin-C-TREM2 pathway protect against tau pathology and other

neurodegeneration | 2026-04-25 | 13 hypotheses Top: 0.867

Does C1q function differ based on subcellular localization or binding partner id

neurodegeneration | 2026-04-25 | 6 hypotheses Top: 0.750

Gene Co-expression Network Analysis of AD Progression Modules

neurodegeneration | 2026-04-16 | 1 hypotheses Top: 0.844

Is C1q elevation in AD pathogenic or compensatory for amyloid clearance?

neurodegeneration | 2026-04-12 | 0 hypotheses

Experiments (11)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Mobile App-Based Intervention for BPSD in Community-Dwelling Dementia	clinical	dementia with behavioral and p	0.950	0.00	human patients	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

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
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
Complement and microglia mediate early synapse loss in Alzheimer mouse models. [PMID:27033548]	Hong S, Beja-Glasser VF, Nfonoyim BM, Fr	Science	2016	1
First-in-Human Phase I Study of KPT-9274, a First-in-Class Dual Inhibitor of PAK [PMID:41824279]	["Razak A", "Mahipal A", "Diamond JR", "	Target Oncol	2026	0
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 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
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
The cholesterol 24-hydroxylase CYP46A1 promotes α-synuclein pathology in Parkins [PMID:39964974]	Dai L, Wang J, Meng L, Zhang X, Xiao T,	PLoS biology	2025	0
PDE4 inhibition alleviates HMGB1/C1q/C3-mediated excessive phagocytic pruning of [PMID:39947489]	Zhao Q, Zeng C, Luo F, Xian Z, Wen H, Tu	Brain, behavior, and immunity	2025	0
Botulinum Neurotoxin Induces Neurotoxic Microglia Mediated by Exogenous Inflamma [PMID:38342616]	Ambrin G, Kang YJ, Van Do K, Lee C, Sing	Advanced science (Weinheim, Ba	2024	0
Development of Injectable Thermosensitive Nanocomposite Hydrogel for Ratiometric [PMID:38456789]	["Zhu J", "Wei R", "Hu G", "Wang H", "Wa	Small (Weinheim an der Bergstr	2024	0
The Role of Complement Dysregulation in Glaucoma. [PMID:38396986]	["Hoppe C", "Gregory-Ksander M"]	International journal of molec	2024	0
Retracted: Ginsenoside Rg1 Ameliorates Acute Renal Ischemia/Reperfusion Injury v [PMID:38234567]	["Longevity O"]	Oxidative medicine and cellula	2024	0
Role of neuroinflammation in neurodegeneration development. [PMID:37433768]	Zhang W, Xiao D, Mao Q, Xia H	Signal transduction and target	2023	0
Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy. [PMID:36890231]	Chen X, Firulyova M, Manis M, Herz J, Sm	Nature	2023	0

Debates (12)

Multi-agent debates referencing this entity

Test question for preregistration

closed · Rounds: 4 · Score: 0.77 · 2026-04-28

Hypothesis debate: SASP-Mediated Complement Cascade Amplification

closed · Rounds: 4 · Score: 0.40 · 2026-04-27

Does the cancer-cystatin-C-TREM2 pathway protect against tau pathology and other

closed · Rounds: 4 · Score: 0.66 · 2026-04-25

Does C1q function differ based on subcellular localization or binding partner id

closed · Rounds: 4 · Score: 0.68 · 2026-04-25

What is the role of microglial synaptic pruning in Alzheimer's disease and other

closed · Rounds: 4 · Score: 0.68 · 2026-04-22

What co-expression modules are shared and unique across brain regions in AD, and

closed · Rounds: 4 · Score: 0.70 · 2026-04-21

The debate aimed to cross-reference Allen Aging Mouse Brain Atlas data with huma

closed · Rounds: 4 · Score: 0.50 · 2026-04-18

Is TYROBP a genuine therapeutic target in AD, or is it a downstream marker of mi

closed · Rounds: 4 · Score: 0.70 · 2026-04-16

The debate revealed conflicting evidence about C1q's role - some studies show it

closed · Rounds: 4 · Score: 0.58 · 2026-04-16

Senolytics targeting p16/p21+ senescent astrocytes and microglia may reduce SASP

closed · Rounds: 4 · Score: 0.89 · 2026-04-06

Related Research

Hypotheses and analyses mentioning complement cascade in their description or question text

H2: Perforant Path Synapse Loss via Early Complement Cascade Activation

Score: 0.610 · neurodegeneration · 2026-04-22

## Mechanistic Overview H2: Perforant Path Synapse Loss via Early Complement Cascade Activation starts from the claim th

TNF-α–C1r/C1s Bridge Between NF-κB and Classical Complement Cascade

Score: 0.600 · neuroinflammation · 2026-04-21

**Molecular Mechanism and Rationale** The TNF-α–C1r/C1s bridge represents a critical mechanistic link connecting cytoki

Timed Senolytic Therapy Eliminates p16^Ink4a/p21^Cip1-Senescent Microglia to Pre

Score: 0.564 · neuroinflammation · 2026-04-15

## Mechanistic Overview Timed Senolytic Therapy Eliminates p16^Ink4a/p21^Cip1-Senescent Microglia to Prevent SASP-Driven

Combined NAMPT-Alectinib Targeting of SASP-Complement Cascade

Score: 0.549 · neuroinflammation · 2026-04-16

## Mechanistic Overview Combined NAMPT-Alectinib Targeting of SASP-Complement Cascade starts from the claim that modulat