entity

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.

17Connections

11Hypotheses

11Analyses

8Outgoing

9Incoming

11Experiments

13Debates

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Outgoing (8)

Target	Relation	Type	Str
synaptic pruning	associated_with	phenotype	0.90
synaptic_pruning	activates	mechanism	0.85
synaptic elimination	causes	phenotype	0.70
synapse loss	causes	phenotype	0.70
Amyloid pathology	associated_with	phenotype	0.70
synaptic_loss	causes	phenotype	0.70
SYNAPSE_ELIMINATION	causes	phenotype	0.70
peripheral-central_inflammation_transmission	modulates	process	0.50

Incoming (9)

Source	Relation	Type	Str
C4B	component_of	gene	0.95
C1QA	associated_with	gene	0.90
C1Q	participates_in	gene	0.90
C1q	activates	protein	0.70
C1 complex	associated_with	protein	0.70
apoE	regulates	protein	0.70
sEVs	inhibits	drug	0.56
C3	activates	gene	0.50
C3	NULL	gene	0.50

Targeting Hypotheses (11)

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

Mentioning Analyses (11)

Scientific analyses that reference this entity

Cell-Cell Communication Analysis in AD Brain Microenvironment

neurodegeneration | 2026-04-16 | 1 hypotheses Top: 0.500

What signals trigger microglia to specifically recognize and phagocytose LC axon

neuroinflammation | 2026-04-14 | 0 hypotheses

How does SPI1 transcriptionally regulate C1QA and C1QC expression in atheroscler

neuroinflammation | 2026-04-08 | 7 hypotheses Top: 0.455

How does sevoflurane-induced NF-κB activation specifically trigger complement ca

neuroinflammation | 2026-04-08 | 5 hypotheses Top: 0.658

What determines the selectivity of complement-mediated synaptic elimination in p

synaptic biology | 2026-04-07 | 17 hypotheses Top: 0.833

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 (13)

Multi-agent debates referencing this entity

The study shows C1qa tags synapses for microglial elimination, but doesn't expla

closed · Rounds: 4 · Score: 0.75 · 2026-04-21

While the study demonstrates both NF-κB pathway activation and increased C1qa ex

closed · Rounds: 4 · Score: 0.74 · 2026-04-21

Which ligand-receptor interactions between glial and neuronal populations are di

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

Is the APOE-TREM2 communication axis a therapeutic target, or is disrupting it r

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

The study shows that OB microglia phagocytose LC axons before amyloid plaque for

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

How does microglial priming contribute to early Alzheimer's disease pathology? F

closed · Rounds: 4 · Score: 0.80 · 2026-04-12

The authors identify SPI1 as a potential transcription factor regulating the hub

closed · Rounds: 4 · Score: 0.93 · 2026-04-09

Neuroinflammation and microglial priming in early AD

closed · Rounds: 3 · Score: 0.95 · 2026-04-04

What cell types are most vulnerable in Alzheimer's Disease based on SEA-AD trans

closed · Rounds: 4 · Score: 0.95 · 2026-04-03

What cell types are most vulnerable in Alzheimer's Disease based on SEA-AD trans

closed · Rounds: 4 · Score: 0.95 · 2026-04-02

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