concept

SYNAPSE

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about SYNAPSE: 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.

1716Connections

16Hypotheses

1Analyses

50Outgoing

50Incoming

10Experiments

1Debates

Summary

SYNAPSE is a concept in neurodegeneration research. Key relationships include: regulates, activates, associated with. Associated with ALS, Aging, Als. Connected to 572 entities in the SciDEX knowledge graph.

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💡 Concept Info

Name	SYNAPSE
Key Genes/Proteins	ACHE, Actin, adnp, ADNP, AD RISK GENES, AEP
Related Diseases	aging, Aging
Related Pathways	Akt

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

Synapse Elimination in Neurodegeneration

mechanism · 3142 words

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Pathway Diagram

graph TD
    SYNAPSE["SYNAPSE"]
    SYNAPSE -->|"regulates"| Parkinson["Parkinson"]
    SYNAPSE -->|"regulates"| Prion_Disease["Prion Disease"]
    SYNAPSE -->|"regulates"| Huntington["Huntington"]
    SYNAPSE -->|"regulates"| Alzheimer["Alzheimer"]
    SYNAPSE -->|"regulates"| NEURODEGENERATIVE_DISORDERS["NEURODEGENERATIVE DISORDERS"]
    SYNAPSE -->|"regulates"| HUNTINGTON["HUNTINGTON"]
    SYNAPSE -->|"regulates"| Cell_Cycle["Cell Cycle"]
    BDNF["BDNF"] -->|"expressed in"| SYNAPSE
    Complement["Complement"] -->|"activates"| SYNAPSE
    PI3K["PI3K"] -->|"regulates"| SYNAPSE
    AKT["AKT"] -->|"regulates"| SYNAPSE
    SNCA["SNCA"] -->|"regulates"| SYNAPSE
    NDUFA9["NDUFA9"] -->|"regulates"| SYNAPSE
    GENES["GENES"] -->|"regulates"| SYNAPSE
    ALZHEIMER["ALZHEIMER"] -->|"regulates"| SYNAPSE
    TUBB3["TUBB3"] -->|"regulates"| SYNAPSE

Outgoing (1001)

Target	Relation	Type	Str
Als	activates	disease	1.00
Neurodegeneration	activates	disease	1.00
Alzheimer	associated_with	disease	0.95
NEURODEGENERATIVE_DISEASES	associated_with	disease	0.90
ALZHEIMER'S_DISEASE	associated_with	disease	0.90
ALZHEIMER'S_DISEASE	disrupts	disease	0.90
Alzheimer	causes	disease	0.85
Als	associated_with	disease	0.85
Als	therapeutic_target	disease	0.85
Neuroinflammation	activates	disease	0.85
Alzheimer	activates	disease	0.85
Alzheimer	regulates	disease	0.85
Alzheimer	therapeutic_target	disease	0.85
Inflammation	activates	disease	0.85
Inflammation	associated_with	disease	0.85
COGNITIVE_DECLINE	causes	disease	0.80
Complement	activates	pathway	0.80
Complement	inhibits	pathway	0.80
Aging	therapeutic_target	disease	0.75
Neurodegeneration	regulates	disease	0.75
Neuroinflammation	regulates	disease	0.75
Neurodegeneration	associated_with	disease	0.75
Parkinson	expressed_in	disease	0.75
Aging	biomarker_for	disease	0.75
Inflammation	regulates	disease	0.75
Neuroinflammation	inhibits	disease	0.75
Inflammation	inhibits	disease	0.75
Als	expressed_in	disease	0.75
Aging	associated_with	disease	0.75
Aging	expressed_in	disease	0.75
Alzheimer	inhibits	disease	0.75
Neuroinflammation	associated_with	disease	0.75
Neurodegeneration	causes	disease	0.75
Huntington	regulates	disease	0.75
Depression	associated_with	disease	0.75
Depression	regulates	disease	0.75
ALZHEIMER'S DISEASE	associated_with	gene	0.70
EPILEPSY	associated_with	disease	0.70
ALZHEIMER	associated_with	gene	0.70
Complement	regulates	pathway	0.70
ALZHEIMER	activates	gene	0.70
AUTOPHAGY	associated_with	pathway	0.70
MITOPHAGY	part_of	pathway	0.70
TAU	associated_with	gene	0.70
MICROGLIA	activates	gene	0.70
PROINFLAMMATORY CYTOKINES	activates	gene	0.70
ASTROCYTE_SYNAPSE_CONTACT	part_of	pathway	0.70
Frontotemporal Dementia	activates	disease	0.65
ALS	associated_with	disease	0.65
Prion Disease	regulates	disease	0.65

Incoming (715)

Source	Relation	Type	Str
NEURODEGENERATION	activates	gene	1.00
NEUROINFLAMMATION	activates	gene	0.80
C1Q	activates	gene	0.80
ALZHEIMER	associated_with	gene	0.80
ALZHEIMER	causes	gene	0.80
DEPRESSION	associated_with	gene	0.80
C1Q	inhibits	gene	0.80
ALZHEIMER'S DISEASE	associated_with	gene	0.80
TAU	activates	gene	0.80
NEURODEGENERATIVE DISEASES	activates	gene	0.80
ALZHEIMER'S DISEASE	regulates	gene	0.80
NEURON	activates	gene	0.80
COMPLEMENT	inhibits	gene	0.80
GENES	associated_with	gene	0.80
ALZHEIMER	regulates	gene	0.80
CX3CR1	associated_with	gene	0.75
MICROGLIA	associated_with	gene	0.75
BDNF	expressed_in	protein	0.72
CYTOKINES	activates	gene	0.70
MICROGLIA	activates	gene	0.70
PARKINSON'S DISEASE	expressed_in	gene	0.70
NEURON	causes	gene	0.70
ARC	regulates	gene	0.70
ALZHEIMER	inhibits	gene	0.70
NEURON	interacts_with	gene	0.70
SYNAPTOPHYSIN	inhibits	gene	0.70
AGING	associated_with	gene	0.70
AMYLOID	activates	gene	0.70
COMPLEMENT	activates	gene	0.70
PARKINSON	expressed_in	gene	0.70
NEURODEGENERATION	regulates	gene	0.70
DEPRESSION	regulates	gene	0.70
MICROGLIA	regulates	gene	0.70
ASTROCYTES	inhibits	gene	0.70
ALZHEIMER'S DISEASE	activates	gene	0.70
NEURODEGENERATION	associated_with	gene	0.70
NEUROINFLAMMATION	associated_with	gene	0.70
NEURON	associated_with	gene	0.70
ALZHEIMER'S DISEASE	inhibits	gene	0.70
Complement	activates	entity	0.70
COMPLEMENT	regulates	gene	0.70
Complement	inhibits	entity	0.70
NEURODEGENERATIVE DISEASES	associated_with	gene	0.70
ASTROCYTES	associated_with	gene	0.70
PARKINSON	associated_with	gene	0.70
GENES	expressed_in	gene	0.70
NEURON	expressed_in	gene	0.70
ALZHEIMER	therapeutic_target	gene	0.70
PI3K	activates	gene	0.70
ALZHEIMER'S DISEASE	therapeutic_target	gene	0.70

Targeting Hypotheses (16)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
H1: TREM2 Agonism to Redirect APOE4-Enhanced Microglia from	0.887	neurodegeneration	How does APOE4's beneficial immune funct
CX3CR1-TREM2 Integration for Synapse Pruning Normalization	0.776	neurodegeneration	TREM2 agonism vs antagonism in DAM micro
SASP-Mediated Cholinergic Synapse Disruption	0.763	neurodegeneration	Senolytic therapy for age-related neurod
TBK1 Loss-of-Function Amplifies C1q-Mediated Synapse Elimina	0.724	neurodegeneration	How do the seven novel ALS genes functio
C1q has spatially distinct functions, with synapse-bound C1q	0.630	neurodegeneration	Does C1q function differ based on subcel

Cross-Cell Type Synaptic Rescue via Tripartite Synapse Resto	0.620	neurodegeneration	Cell type vulnerability in Alzheimer's D
H2: Perforant Path Synapse Loss via Early Complement Cascade	0.610	neurodegeneration	Entorhinal cortex layer II vulnerability
Aberrant Galectin-3 Expression on Stressed Synapses Creates	0.600	synaptic biology	What determines the selectivity of compl
Activity-dependent MAP6 scaffolding at synapses	0.600	neurodegeneration	View
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
TFEB Activation to Restore Lysosomal Biogenesis in Aged Syna	0.533	proteomics	Quantitative proteomics of the aging syn
C1q shows synapse-class-specific roles, with inhibitory vers	0.530	neurodegeneration	Does C1q function differ based on subcel
Dysregulated microglial glycolysis via HIF1α activation shif	0.520	neurodegeneration	Synaptic pruning by microglia in neurode
Tripartite Synapse Cell Type-Nonautonomous Crosstalk: Coordi	0.510	neurodegeneration	Cell type vulnerability debate in Alzhei
Astrocyte Heterogeneity and Synapse-Specific Eat-Me Signal E	0.490	synaptic biology	What determines the selectivity of compl

Mentioning Analyses (1)

Scientific analyses that reference this entity

Protein aggregation cross-seeding across neurodegenerative diseases

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.639

Experiments (10)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Endothelium-specific TBK1 knockdown in atherosclerosis model	validation	atherosclerosis	0.900	0.00	endothelium-specific TBK1 knoc	proposed	N/A
TBK1-PAK1IP1-PAK1 signaling pathway analysis	exploratory	atherosclerosis	0.900	0.00	endothelial cells	proposed	N/A
LPS-induced mouse model of depression with synaptic loss analysis	validation	depression	0.900	0.00	LPS-treated mice	proposed	N/A
Bidirectional Mendelian randomization analysis of C1Q and ischemic str	exploratory	Ischemic stroke, Atheroscleros	0.900	0.00	Human genetic association data	proposed	N/A
Bidirectional Mendelian randomization analysis of C1Q and ischemic str	exploratory	Ischemic stroke (large artery	0.900	0.00	human genetic data	proposed	N/A
C1q neutralizing antibody intervention in depression model	validation	depression	0.850	0.00	LPS-treated mice with C1q anti	proposed	N/A
GSK8612 treatment in atherosclerosis model	validation	atherosclerosis	0.800	0.00	atherosclerosis mouse model	proposed	N/A
LC-MS/Western blot analysis of TBK1 in atherosclerotic arteries	exploratory	atherosclerosis	0.800	0.00	mouse and human arteries with	proposed	N/A
Cholinergic System Dysfunction in DLB — Mechanisms and Therapeutic Res	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
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
Clinical, Immunological, and Vesicular Markers in Sarcopenia and Presarcopenia. [PMID:40917056]	Shuliko LM, Svarovsky DA, Spirina LV, Og	Front Biosci (Landmark Ed)	2025	1
CD47-blocking antibody interferes with neutrophil extracellular traps formation [PMID:39951937]	Diao Y, Hao M, Xie M, Hu X, Tan R, Wang	J Neuroimmunol	2025	1
Asparagine Endopeptidase Inhibition Attenuates Tissue Plasminogen Activator-Indu [PMID:40116141]	Xie G, Jiang G, Huang L, Sun S, Li X, Wu	CNS Neurosci Ther	2025	1
Enhanced anticancer activity of nanoemulsified cardamom extract via modulation o [PMID:41658858]	["Soltani T", "Karimian M", "Vaziri H",	Biochemistry and biophysics re	2026	0
Restricting intracellular Salmonella proliferation by coordinating p-TBK1 mediat [PMID:40660474]	Li J, Yang Y, Ge Y, Zhang X, Liu H et al	Autophagy	2026	0
Aberrant STING signalling promotes endothelial dysfunction and neurovascular inj [PMID:41419617]	Qin X, Chen S, Sun Y, Ma Z, Niu C et al.	Diabetologia	2026	0
TBK1 orchestrates autophagy and endo-lysosomal pathways in human neurons. [PMID:41485128]	Mordes DA, Smeyers J	Autophagy	2026	0
Dynamic regulation of TBK1 lactylation shapes antiviral immune responses. [PMID:41530535]	Xie Y, Zhang Y, Peng W, Zhang L, Hu Z et	Cell Mol Immunol	2026	0
Peripheral cancer attenuates amyloid pathology in Alzheimer's disease via cystat [PMID:41576952]	Li X, Tang X, Zeng J, Duan L, Hou Z et a	Cell	2026	0
RIG-I Mediated Neuron-Specific IFN Type 1 Signaling in FUS-ALS Induces Neurodege [PMID:41603250]	Naumann M, Wierschin TM, Kretschmer S, D	Adv Sci (Weinh)	2026	0
BTK inhibition suppresses neuroinflammation and neurodegeneration in amyotrophic [PMID:41710977]	Liu Q, Zhang X, Wang L, Chen H, Wang G e	Brain	2026	0
Systematic Review: Porphyromonas gingivalis Outer Membrane Vesicles From Pathoge [PMID:41980468]	Li Z, Luo C, Wen P, Zou T, Jin Z et al.	Int Dent J	2026	0
Integrated transcriptomic, proteomic, and metabolomic analyses reveal molecular [PMID:41850064]	["Wang H", "Liu Y", "Jiang K", "Yin J",	Poultry science	2026	0
TBK1 orchestrates autophagy and endo-lysosomal pathways in human neurons. [PMID:41485128]	Mordes DA, Smeyers J	Autophagy	2026	0
Fragment merging design, synthesis, and biological evaluation of novel methyl Se [PMID:41785527]	["Shaaban S", "Hawas S", "Elmaaty A", "B	Bioorganic & medicinal chemist	2026	0
Theranekron modulates extracellular matrix and apoptotic signaling pathways in c [PMID:41852375]	["Kuccukturk S", "Duran T", "Vanli S", "	Cytotechnology	2026	0
BTK inhibition suppresses neuroinflammation and neurodegeneration in amyotrophic [PMID:41710977]	Liu Q, Zhang X, Wang L, Chen H, Wang G,	Brain : a journal of neurology	2026	0
Saliva liquid biopsy: MMP2, MMP9, and TIMP2 as potential diagnostic biomarkers i [PMID:41779471]	["Cruz-Romero S", "Baldi\u00f3n A", "Taw	Journal of applied oral scienc	2026	0
Glomerular Transcriptome Analysis Reveals Endothelial Disturbances in Patients W [PMID:41659822]	["Nelson-Taylor S", "Troost J", "Giannin	Kidney medicine	2026	0
Encapsulation of hydroxyurea in exosomes derived from adipose mesenchymal stem c [PMID:41702234]	["Taheri Kangarshahi Z", "Ganji S", "Ash	Translational oncology	2026	0

Debates (1)

Multi-agent debates referencing this entity

What are the mechanisms underlying protein aggregation cross-seeding across neur

closed · Rounds: 4 · Score: 0.95 · 2026-04-01

Related Research

Hypotheses and analyses mentioning SYNAPSE in their description or question text

SYNAPSE

Understanding Entity Pages

Summary

Wiki Pages (1)

Synapse Elimination in Neurodegeneration

Pathway Diagram

Outgoing (1001)

Incoming (715)

Targeting Hypotheses (16)

Mentioning Analyses (1)

Protein aggregation cross-seeding across neurodegenerative diseases

Experiments (10)

Related Papers (20)

Debates (1)

What are the mechanisms underlying protein aggregation cross-seeding across neur

Related Research

Cross-Cell Type Synaptic Rescue via Tripartite Synapse Restoration

H2: Perforant Path Synapse Loss via Early Complement Cascade Activation

Aberrant Galectin-3 Expression on Stressed Synapses Creates Bridging Molecules

Activity-dependent MAP6 scaffolding at synapses

TREM2-C1Q Competitive Binding to Prevent Complement-Mediated Cholinergic Synapse

H5: Complement Dysregulation Drives Synapse Loss via Senescent APOE4 Astrocytes

TFEB Activation to Restore Lysosomal Biogenesis in Aged Synapses

C1q shows synapse-class-specific roles, with inhibitory versus excitatory synaps

Dysregulated microglial glycolysis via HIF1α activation shifts the balance from

Tripartite Synapse Cell Type-Nonautonomous Crosstalk: Coordinated Failure

Astrocyte Heterogeneity and Synapse-Specific Eat-Me Signal Expression