entity

Signaling

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about Signaling: 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.

3Connections
30Hypotheses
0Analyses
0Outgoing
3Incoming
14Experiments
0Debates

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Wiki Pages (20)

Knowledge base pages for this entity

Neurotrophin Signaling Pathways in Neurodegeneration

mechanism · 4695 words

Wnt Non-Canonical Signaling Pathways in Neurodegeneration

mechanism · 4664 words

TREM2 Microglial Signaling Pathway in Neurodegeneration

mechanism · 4613 words

Vitamin D Signaling Pathway in Neurodegeneration

mechanism · 4520 words

CREB Signaling in Neurodegeneration

mechanism · 4156 words

Outgoing (0)

TargetRelationTypeStr
No outgoing edges

Incoming (3)

SourceRelationTypeStr
Ubiquitin-Proteasome Systemregulatespathway0.95
E3 Ubiquitin Ligasesregulatesenzyme0.95
UPSregulatespathway0.95

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

HypothesisScoreDiseaseAnalysis
IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microgl 0.831 neuroinflammation How do oligodendrocytes initiate neuroin
Microglial-Mediated Tau Clearance Dysfunction via TREM2 Sign 0.827 neuroscience Circuit-level neural dynamics in neurode
Beta-Hydroxybutyrate Receptor (HCAR2) Signaling Links Ketone 0.808 neurodegeneration What are the precise temporal dynamics o
Hypothesis 1: MANF/CDNF Signaling as Primary Neuroprotective 0.798 neurodegeneration View
Direct Toxicity Hypothesis: β-Amyloid Directly Impairs Choli 0.769 - Do β-amyloid plaques and neurofibrillary
TREM2-Dependent Switch Hypothesis: TREM2 Agonism Redirects S 0.753 synaptic biology Does SPP1-mediated synaptic engulfment r
Astrocyte C3aR Signaling as Bifurcation Point for A1/A2 Fate 0.749 Alzheimer's disease, Parkinson's disease -
Purinergic Signaling Polarization Control 0.713 neurodegeneration Astrocyte reactivity subtypes in neurode
Astrocytic-Mediated Tau Clearance Dysfunction via TREM2 Sign 0.672 neuroscience Circuit-level neural dynamics in neurode
Fyn-anchored dendritic tau/NMDAR signaling persists after tr 0.670 neurodegeneration Does tau dendritic missorting persist in
Leaky Gut LPS Translocation Activates Systemic TLR4/MyD88 Si 0.670 neurodegeneration How does gut microbiome dysbiosis contri
Dissociating SCFA's Dual Signaling Through GPR43/GPR41 Biase 0.670 neurodegeneration Do SCFAs directly modulate α-synuclein a
Enhancing Vagal Cholinergic Signaling to Restore Gut-Brain A 0.669 neurodegeneration What are the mechanisms by which gut mic
Chronic cGAS/STING Hyperactivation Drives Progressive Neurod 0.661 neuroinflammation How does chronic cGAS/STING activation d
Parthenolide reduces tonic ADORA2A signaling by lowering inf 0.659 neuropharmacology How does parthenolide specifically modul
Gamma entrainment enhances TREM2-mediated microglial clearan 0.653 Alzheimer's disease Gamma entrainment therapy to restore hip
Age-Dependent TREM2 Signaling Disrupts Astrocyte-Microglia C 0.649 neurodegeneration Gene expression changes in aging mouse b
Activity-Dependent Synaptic Tagging via CREB-BDNF-TrkB Signa 0.646 synaptic biology What determines the selectivity of compl
Retromer-dependent retrograde endosomal signaling compartmen 0.645 neuroscience How can subcellular compartmentalization
Layer V excitatory neurons show selectively enhanced vulnera 0.632 Alzheimer's disease SEA-AD Single-Cell Analysis: Cell-Type V
C1q has spatially distinct functions, with synapse-bound C1q 0.630 neurodegeneration Does C1q function differ based on subcel
APOE4-microglial complement signaling causes cholinergic-enr 0.630 neurodegeneration What determines the temporal sequence of
CCL2-CCR2 myeloid signaling as a selective driver of fast-fa 0.626 neurodegeneration CCL2-CCR2 Axis at NMJ: Mechanism of Sele
mutant FUS effects split between motor-neuron intrinsic stre 0.626 neurodegeneration Cell-Autonomous vs Non-Cell-Autonomous M
ATF4-DDIT3 stress signaling indirectly represses MAPT transc 0.624 neurodegeneration Which specific transcription factors med
LPS-TLR4-NF-κB Signaling Cascade as Therapeutic Target 0.619 neurodegeneration Gut-Brain Axis in Parkinson's Disease: M
PDGF-BB/PDGFRβ/STAT3 Paracrine Signaling Axis Mediates Aβ-In 0.618 neurodegeneration How do perivascular cells specifically r
Blocking AGE-RAGE Signaling in Enteric Glia to Prevent Neuro 0.613 neurodegeneration What are the mechanisms by which gut mic
TREM2-Mediated Oligodendrocyte-Microglia Signaling in White 0.587 neurodegeneration Gene expression changes in aging mouse b
TBK1 Loss Triggers Astrocyte-to-Neuron Senescence Propagatio 0.000 ALS What are the mechanisms by which microgl

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (14)

Experimental studies targeting or related to this entity

ExperimentTypeDiseaseScoreFeasibilityModelStatusEst. Cost
PINK1 mutation carriers frequently report experiencing pain. genetic_association Parkinson's disease 0.500 0.00 human extracted N/A
Evidence regarding pain in DNAJC6 pathogenic variants is limited and i genetic_association Parkinson's disease 0.500 0.00 human extracted N/A
Identification of a vulnerable subtype of dopaminergic neurons co-expr genetic_association Parkinson's disease 0.500 0.00 mouse extracted N/A
Evidence regarding pain in SYNJ1 pathogenic variants is limited and in genetic_association Parkinson's disease 0.500 0.00 human extracted N/A
Anxa1+ DANs show selective earlier loss compared to other dopaminergic neuropathology Parkinson's disease 0.500 0.00 mouse extracted N/A
Released prosaposin (PSAP) was shown to induce interleukin-6 (IL-6) up cell_biology Parkinson's disease 0.500 0.00 cell_culture extracted N/A
Evidence regarding pain in FBXO7 pathogenic variants is limited and in genetic_association Parkinson's disease 0.500 0.00 human extracted N/A
Evidence regarding pain in ATP13A2 pathogenic variants is limited and genetic_association Parkinson's disease 0.500 0.00 human extracted N/A
Inhibition of transmitter release specifically in Anxa1+ neurons was s animal_model Parkinson's disease 0.500 0.00 mouse extracted N/A
Identified a subtype of Sox6+ Anxa1+ dopaminergic neurons that are sel neuropathology Parkinson's disease 0.500 0.00 mouse extracted N/A
s:** - GPR32 knockout in microglia should worsen neuroinflammation if falsification Neuroinflammation 0.400 0.50 cell_line proposed $80,000
Proposed experiment from debate on Synaptic pruning by microglia in ea falsification Neuroinflammation 0.400 0.50 mouse proposed $240,000
Endocannabinoid System Dysfunction Validation in Parkinson's Disease clinical Parkinson's Disease 0.400 0.50 human proposed $6,550,000
Purinergic Signaling Dysfunction Validation in Parkinson's Disease clinical Parkinson's Disease 0.400 0.50 human proposed $5,460,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMIDAuthorsJournalYearCitations
Oligodendrocytes drive neuroinflammation and neurodegeneration in Parkinson's di [PMID:39913287] Ma Q, Tian JL, Lou Y, Guo R, Ma XR, Wu J Cell Rep 2025 1
Purinergic signaling elements are correlated with coagulation players in periphe [PMID:35091759] Schultz IC, Bertoni APS, Wink MR J Mol Med (Berl) 2022 1
Purinergic Receptors in the Airways: Potential Therapeutic Targets for Asthma? [PMID:35386996] Thompson RJ, Sayers I, Kuokkanen K, Hall Front Allergy 2021 1
Variation in glucose homeostasis traits associated with P2RX7 polymorphisms in m [PMID:25719930] Todd JN, Poon W, Lyssenko V, Groop L, Ni J Clin Endocrinol Metab 2015 1
Targeting Microglial Phagocytosis for Alzheimer's Disease Management: Natural, P [PMID:40641018] Raghuvanshi S, Mazumder A, Das S CNS & neurological disorders d 2026 0
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810] ["Chen Kai", "Li Fuyao", "Zhang Shuwen", Journal of neuroinflammation 2025 0
The APOE-Microglia Axis in Alzheimer's Disease: Functional Divergence and Therap [PMID:40722268] Unknown Brain sciences 2025 0
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810] ["Chen Kai", "Li Fuyao", "Zhang Shuwen", Journal of neuroinflammation 2025 0
Axonal injury is a targetable driver of glioblastoma progression. [PMID:40836081] Clements M, Tang W, Florjanic Baronik Z, Nature 2025 0
Soluble CSF1R promotes microglial activation and amyloid clearance in alzheimer' [PMID:41152873] Zhang L, Chen K, Zeng R J Neuroinflammation 2025 0
CSF ATP levels correlate with Alzheimer's disease severity and predict progressi [PMID:synthetic_4] Unknown JAMA Neurol 2024 0
Delivery of CDNF by AAV-mediated gene transfer protects dopamine neurons and reg [PMID:39019902] Nam J, Richie CT, Harvey BK Sci Rep 2024 0
Astrocyte phenotype switching controlled by purinergic receptor balance regulate [PMID:synthetic_1] Unknown Nature Neuroscience 2023 0
α7nAChR activation in AT2 cells promotes alveolar regeneration through WNT7B sig [PMID:37410546] Unknown JCI Insight 2023 0
P2Y1 agonist enhances astrocyte-mediated neuroprotection via BDNF upregulation [PMID:synthetic_3] Unknown Glia 2023 0
Astrocyte phenotype heterogeneity may not fit simple A1/A2 binary classification [PMID:synthetic_8] Unknown Cell 2023 0
Untangling the Role of TREM2 in Conjugation with Microglia in Neuronal Dysfuncti [PMID:36683512] Basha SC, Ramaiah MJ, Kosagisharaf JR J Alzheimers Dis 2023 0
P2X7 antagonists failed to show efficacy in depression trials despite target eng [PMID:synthetic_6] Unknown Mol Psychiatry 2022 0
P2X7 antagonist reduces amyloid pathology and preserves cognition in APP/PS1 mic [PMID:synthetic_2] Unknown Neurobiol Dis 2022 0
JNJ-47965567 P2X7 antagonist shows CNS penetration and safety in Phase 2 trial [PMID:synthetic_5] Unknown Lancet Psychiatry 2021 0

Debates (0)

Multi-agent debates referencing this entity

No debates reference this entity

Related Research

Hypotheses and analyses mentioning Signaling in their description or question text

TREM2-Dependent Switch Hypothesis: TREM2 Agonism Redirects SPP1 Signaling from D

Score: 0.753 · synaptic biology · 2026-04-21

## Mechanistic Overview TREM2-Dependent Switch Hypothesis: TREM2 Agonism Redirects SPP1 Signaling from Destructive to Re

Purinergic Signaling Polarization Control

Score: 0.713 · neurodegeneration · 2026-04-02

## Mechanistic Overview Purinergic Signaling Polarization Control starts from the claim that modulating P2RY1 and P2RX7

Astrocytic-Mediated Tau Clearance Dysfunction via TREM2 Signaling

Score: 0.672 · neuroscience · 2026-04-12

## **Molecular Mechanism and Rationale** The astrocytic-mediated tau clearance dysfunction hypothesis centers on the pa

Fyn-anchored dendritic tau/NMDAR signaling persists after transient Aβ exposure

Score: 0.670 · neurodegeneration · 2026-04-25

Aβ drives tau into dendritic spines, where tau binds Fyn and stabilizes a PSD95-NMDAR-associated excitotoxic scaffold. O

Leaky Gut LPS Translocation Activates Systemic TLR4/MyD88 Signaling, Driving CNS

Score: 0.670 · neurodegeneration · 2026-04-26

Dysbiosis compromises intestinal tight junctions (occludin, claudin-1, ZO-1) and reduces α-defensin production, permitti

Dissociating SCFA's Dual Signaling Through GPR43/GPR41 Biased Agonism

Score: 0.670 · neurodegeneration · 2026-04-13

## Mechanistic Overview Dissociating SCFA's Dual Signaling Through GPR43/GPR41 Biased Agonism starts from the claim that

Enhancing Vagal Cholinergic Signaling to Restore Gut-Brain Anti-Inflammatory Com

Score: 0.669 · neurodegeneration · 2026-04-02

## Mechanistic Overview Enhancing Vagal Cholinergic Signaling to Restore Gut-Brain Anti-Inflammatory Communication start

Chronic cGAS/STING Hyperactivation Drives Progressive Neurodegeneration Through

Score: 0.661 · neuroinflammation · 2026-04-21

## Mechanistic Overview Chronic cGAS/STING Hyperactivation Drives Progressive Neurodegeneration Through Sustained Type I

Parthenolide reduces tonic ADORA2A signaling by lowering inflammatory extracellu

Score: 0.659 · neuropharmacology · 2026-04-25

NF-kB suppression in glia decreases ectonucleotidase and cytokine programs that sustain extracellular adenosine, indirec

Gamma entrainment enhances TREM2-mediated microglial clearance of Aβ plaques via

Score: 0.653 · Alzheimer's disease · 2026-04-28

40 Hz neural activity induces Ca2+ oscillations in microglia through P2X7 receptor activation, promoting TREM2 phosphory

Age-Dependent TREM2 Signaling Disrupts Astrocyte-Microglia Communication Leading

Score: 0.649 · neurodegeneration · 2026-04-17

**Molecular Mechanism and Rationale** The TREM2 (Triggering Receptor Expressed on Myeloid cells 2) signaling pathway re

Activity-Dependent Synaptic Tagging via CREB-BDNF-TrkB Signaling

Score: 0.646 · synaptic biology · 2026-04-21

**Molecular Mechanism and Rationale** The activity-dependent synaptic tagging mechanism represents a sophisticated neur

Retromer-dependent retrograde endosomal signaling compartmentalization as biomar

Score: 0.645 · neuroscience · 2026-04-26

VPS26/VPS29/VPS35 retromer complex maintains axonal endosomal signaling microdomains controlling TrkB/p75NTR trafficking

Layer V excitatory neurons show selectively enhanced vulnerability through dysre

Score: 0.632 · Alzheimer's disease · 2026-04-04

## Mechanistic Overview Layer V excitatory neurons show selectively enhanced vulnerability through dysregulated calcium