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.

4Connections

10Hypotheses

2Analyses

0Outgoing

4Incoming

11Experiments

2Debates

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Outgoing (0)

Target	Relation	Type	Str
No outgoing edges

Incoming (4)

Source	Relation	Type	Str
C4B	component_of	gene	0.95
C1Q	participates_in	gene	0.90
sEVs	inhibits	drug	0.56
C3	activates	gene	0.50

Targeting Hypotheses (10)

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
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 Activation Bridges Microglial OxPC Sensin	0.419	neuroinflammation	What molecular mechanisms enable microgl

Mentioning Analyses (2)

Scientific analyses that reference this entity

How does SPI1 transcriptionally regulate C1QA and C1QC expression in atheroscler

neuroinflammation | 2026-04-08 | 0 hypotheses

Cell type vulnerability in Alzheimer's Disease (SEA-AD data - v2)

neurodegeneration | 2026-04-03 | 7 hypotheses Top: 0.726

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
Divergent complement system activation in two clinically distinct murine models [PMID:35958570]	["Linzey M", "DiSano K", "Welsh N", "Pac	Frontiers in immunology	2022	0
ATAD3A oligomerization promotes neuropathology and cognitive deficits in Alzheim [PMID:35236834]	Zhao Y, Hu D, Wang R, Sun X, Ropelewski	Nature communications	2022	0

Debates (2)

Multi-agent debates referencing this entity

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

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

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

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

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

Complement Cascade Activation Bridges Microglial OxPC Sensing to Synaptic Vulner

Score: 0.419 · neuroinflammation · 2026-04-13

## Mechanistic Overview Complement Cascade Activation Bridges Microglial OxPC Sensing to Synaptic Vulnerability starts f