concept

CLASSICAL COMPLEMENT CASCADE

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about CLASSICAL 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.

21Connections

15Hypotheses

3Analyses

9Outgoing

12Incoming

20Experiments

4Debates

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💡 Concept Info

Name	CLASSICAL COMPLEMENT CASCADE

Pathway Diagram

graph TD
    CLASSICAL_COMPLEMENT_CASCADE["CLASSICAL COMPLEMENT CASCADE"]
    CLASSICAL_COMPLEMENT_CASCADE -->|"causes"| Demyelination["Demyelination"]
    CLASSICAL_COMPLEMENT_CASCADE -->|"causes"| Granulocyte_Infiltration["Granulocyte Infiltration"]
    CLASSICAL_COMPLEMENT_CASCADE -->|"causes"| Eosinophil_Infiltration["Eosinophil Infiltration"]
    CLASSICAL_COMPLEMENT_CASCADE -->|"causes"| Lymphocyte_Infiltration["Lymphocyte Infiltration"]
    CLASSICAL_COMPLEMENT_CASCADE -->|"causes"| Astrocyte_Injury["Astrocyte Injury"]
    CLASSICAL_COMPLEMENT_CASCADE -->|"activates"| leukocyte_infiltration["leukocyte infiltration"]
    Aquaporin_4_IgG["Aquaporin-4-IgG"] -->|"activates"| CLASSICAL_COMPLEMENT_CASCADE
    AQP4_Ab["AQP4-Ab"] -->|"activates"| CLASSICAL_COMPLEMENT_CASCADE
    C1Q["C1Q"] -->|"activates"| CLASSICAL_COMPLEMENT_CASCADE
    Eculizumab["Eculizumab"] -->|"inhibits"| CLASSICAL_COMPLEMENT_CASCADE
    TREM2["TREM2"] -->|"inhibits"| CLASSICAL_COMPLEMENT_CASCADE
    AQP4_ab["AQP4-ab"] -->|"activates"| CLASSICAL_COMPLEMENT_CASCADE
    AQP4_ANTIBODY["AQP4-ANTIBODY"] -->|"activates"| CLASSICAL_COMPLEMENT_CASCADE

Outgoing (9)

Target	Relation	Type	Str
Synapse Loss	drives	phenotype	0.90
Synapse Loss	contributes_to	phenotype	0.88
Astrocyte Injury	causes	process	0.85
Granulocyte Infiltration	causes	process	0.85
Eosinophil Infiltration	causes	process	0.85
Lymphocyte Infiltration	causes	process	0.85
Demyelination	causes	process	0.85
Synaptic Engulfment	mediates	process	0.85
leukocyte infiltration	activates	process	0.70

Incoming (12)

Source	Relation	Type	Str
Aquaporin-4-IgG	activates	biomarker	0.95
C1Q	activates	protein	0.90
AQP4-ab	activates	biomarker	0.90
Eculizumab	inhibits	drug	0.90
AQP4-ANTIBODY	activates	protein	0.90
AQP4-Ab	activates	protein	0.90
C1Q	activates	protein	0.90
C1q	activates	protein	0.85
APOE	inhibits	protein	0.70
C4B	participates_in	gene	0.68
HDAC3	participates_in	gene	0.45
C1QA	participates_in	gene	0.42

Targeting Hypotheses (15)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Targeting SASP-Complement Amplification Through HIF-1α Downs	0.793	neurodegeneration	What molecular mechanism causes VCP muta
Selective HDAC3 Inhibition with Cognitive Enhancement	0.779	neurodegeneration	Epigenetic reprogramming in aging neuron
C1QA/C1QB Subunit-Specific Inhibition to Block Aberrant PV I	0.747	neurodegeneration	Are interneuron oscillation deficits com
Complement-SASP Amplification Cascade as Mechanistic Link	0.741	neurodegeneration	Why have anti-Aβ clinical trials failed
HDAC3-Selective Inhibition for Clock Reset	0.710	neurodegeneration	Epigenetic clocks and biological aging i

Complement C1q Mimetic Decoy Therapy	0.695	neurodegeneration	Synaptic pruning by microglia in early A
Age-Dependent Complement C4b Upregulation Drives Synaptic Vu	0.671	neurodegeneration	Gene expression changes in aging mouse b
Complement C1q Subtype Switching	0.665	neurodegeneration	4R-tau strain-specific spreading pattern
Complement C1QA Inhibition Synergizes with PV Interneuron Mo	0.659	neurodegeneration	What molecular mechanisms underlie the d
C3aR Blockade Disrupts the Microglial-Astrocyte Feedforward	0.633	neuroinflammation	What molecular mechanisms determine whet
Synaptic Pruning Precision Therapy	0.612	Alzheimer's disease	Neuroinflammation and microglial priming
TNF-α–C1r/C1s Bridge Between NF-κB and Classical Complement	0.600	neuroinflammation	How does sevoflurane-induced NF-κB activ
Complement-Mediated Synaptic Protection	0.580	neurodegeneration	Neuroinflammation and microglial priming
Complement C1q Suppression as Mechanism Linking Exercise Pla	0.560	neurodegeneration	What are the specific circulating factor
Complement Cascade Activation Bridges Microglial OxPC Sensin	0.419	neuroinflammation	What molecular mechanisms enable microgl

Mentioning Analyses (3)

Scientific analyses that reference this entity

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

neurodegeneration | 2026-04-03 | 45 hypotheses Top: 0.990

Epigenetic clocks and biological aging in neurodegeneration

neurodegeneration | 2026-04-01 | 6 hypotheses Top: 0.710

4R-tau strain-specific spreading patterns in PSP vs CBD

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.732

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 Epigenetic clocks and biological ag	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$100,000
Mechanism: Why Does Amyloid Removal Only Slow Decline 27%?	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$7,500,000
Animal Model Comparison for Neurodegenerative Disease Therapeutics	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$7,100,000
Epigenetic Dysregulation in Huntington's Disease — Therapeutic Targeti	validation	Neurodegeneration	0.400	0.50	human	proposed	$3,000,000
Epigenetic Dysregulation Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$7,500,000
Epigenetic Regulation Dysfunction in Alzheimer's and Parkinson's Disea	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$7,500,000
Proposed experiment from debate on Microglia activate astrocytes via I	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$100,000
CRISPR Gene Correction Approaches for CBS/PSP	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
s:** - Compare brain penetration in FcRn+/+ vs FcRn-/- mice with engin	falsification	Neuroinflammation	0.400	0.50	mouse	proposed	$200,000
Proposed experiment from debate on Synaptic pruning by microglia in ea	falsification	Alzheimer's Disease	0.400	0.50	mouse	proposed	$200,000
Experiment: Autoimmune Hypothesis Testing in AD	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
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
Effect of Electronic Prescribing Compared to Paper-Based (Handwritten) Prescribi [PMID:34433219]	Aluga D, Nnyanzi LA, King N, Okolie EA,	Appl Clin Inform	2021	1
Structurally diverse sesquiterpenoids from the aerial parts of Artemisia annua ( [PMID:32891001]	Qin DP, Li HB, Pang QQ, Huang YX, Pan DB	Bioorg Chem	2020	1
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2- [PMID:31932797]	Zhou Y, Song WM, Andhey PS, Swain A, Lev	Nat Med	2020	1
Mycobacterium Abscessus: A Rare Cause of Peri-Ductal Mastitis in Endemic Regions [PMID:32580856]	Shaikh A, Vohra LM	J Coll Physicians Surg Pak	2020	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
The scanning ion conductance microscope for cellular physiology. [PMID:23086993]	Lab MJ, Bhargava A, Wright PT, Gorelik J	Am J Physiol Heart Circ Physio	2013	1
Telomere dysfunction causes sustained inflammation in chronic obstructive pulmon [PMID:21885626]	Amsellem V, Gary-Bobo G, Marcos E, Maitr	Am J Respir Crit Care Med	2011	1
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's diseas [PMID:21102463]	Franke A, McGovern DP, Barrett JC, Wang	Nat Genet	2010	1
HDAC3 Preserves the primordial follicle reserve by epigenetically suppressing fe [PMID:41803516]	["Chen Z", "Guo J", "Gao M", "Wang H", "	Cellular and molecular life sc	2026	0
Repurposing of doxycycline as a novel therapeutic avenue for management of parki [PMID:41925933]	Ali NH, Al-Kuraishy HM, Hussain NR, Al-G	Inflammopharmacology	2026	0
Determination of the effects of [PMID:41823023]	["Yir\u00fcn A", "\u00c7ak\u0131r D", "E	Journal of Alzheimer's disease	2026	0
Discovery of a Covalent HDAC3 Degrader with Excellent Anti-Inflammatory Activity [PMID:41812251]	["Qin H", "Shi Y", "Liu R", "Wang B", "G	Journal of medicinal chemistry	2026	0
Myeloid HDAC3 deletion protects against traumatic optic injury. [PMID:41851071]	Shahror RA, Morris CA, Cunningham A, Chu	Cell death discovery	2026	0
Synaptic pruning genes networks in Alzheimer's disease: correlations with neurop [PMID:40515808]	Sanfilippo C, Castrogiovanni P, Imbesi R	Geroscience	2026	0
HDAC3 mediates retinal endothelial cell metabolic reprogramming and angiogenesis [PMID:41023273]	Mitchell CD, Morris CA, Wild M, Cunningh	Acta Pharmacol Sin	2026	0
Metabolomics identifies riboflavin as a therapeutic agent for acute pancreatitis [PMID:41352543]	Shi Y, Peng J	J Nutr Biochem	2026	0
Histological findings in follow-up liver biopsies up to 15 years after pediatric [PMID:41370831]	Quintero-Bernabeu J, Salcedo-Allende MT,	Liver Transpl	2026	0

Debates (4)

Multi-agent debates referencing this entity

PSP and CBD both involve 4R-tau but produce distinct neuropathological patterns

closed · Rounds: 4 · Score: 0.69 · 2026-04-12

PSP and CBD both involve 4R-tau but produce distinct neuropathological patterns

closed · Rounds: 7 · Score: 0.91 · 2026-04-10

Epigenetic clocks and biological aging in neurodegeneration

closed · Rounds: 4 · Score: 0.93 · 2026-04-06

What gene expression changes in the aging mouse brain predict neurodegenerative

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