concept

DISEASE

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about DISEASE: 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.

2310Connections

30Hypotheses

0Analyses

50Outgoing

50Incoming

6Experiments

0Debates

No summary available yet.

View on Wiki →

AI-generated illustration · click image to enlarge

Regenerate portrait ↻

💡 Concept Info

Name	DISEASE
Key Genes/Proteins	SIRTUINS

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

cross-disease

mechanism · 2063 words

→

Pathway Diagram

graph TD
    DISEASE["DISEASE"]
    autophagy["autophagy"] -.protects against.-> DISEASE
    RAB7A["RAB7A"] -->|"implicated in"| DISEASE
    LRP2["LRP2"] -->|"implicated in"| DISEASE
    ACTB["ACTB"] -->|"implicated in"| DISEASE
    CTSD["CTSD"] -->|"implicated in"| DISEASE
    ATG["ATG"] -->|"implicated in"| DISEASE
    EGFR["EGFR"] -->|"implicated in"| DISEASE
    SREBF1["SREBF1"] -->|"implicated in"| DISEASE
    NADH["NADH"] -->|"implicated in"| DISEASE
    MTORC1["MTORC1"] -->|"implicated in"| DISEASE

Outgoing (663)

Target	Relation	Type	Str
Organ Dysfunction	causes	phenotype	0.95
Rna Defects	associated_with	mechanism	0.95
Synaptic Dysfunction	associated_with	mechanism	0.95
Altered Energy Homeostasis	associated_with	mechanism	0.95
Neuronal Network Dysfunction	associated_with	mechanism	0.95
Pathological Protein Aggregation	associated_with	mechanism	0.95
Cytoskeletal Abnormalities	associated_with	mechanism	0.95
Aberrant Proteostasis	associated_with	mechanism	0.95
Dna Defects	associated_with	mechanism	0.95
Retinopathy	activates	disease	0.50
GRAY MATTER	associated_with	concept	0.50
Chronic Kidney Disease	activates	disease	0.50
IL-6 SIGNALING	associated_with	concept	0.50
IL-6 SIGNALING	inhibits	concept	0.50
PIKFYVE	inhibits	concept	0.50
TREHALOSE	causes	concept	0.50
ENDOPLASMIC RETICULUM	regulates	concept	0.50
COPD	causes	disease	0.50
GLUTAMATE	regulates	concept	0.50
Crohn Disease	activates	disease	0.50
Proteins	regulates	protein	0.50
STEM CELLS	interacts_with	concept	0.50
White Matter	associated_with	process	0.50
Substantia Nigra	causes	entity	0.50
Cognitive Impairment	activates	phenotype	0.50
GLIOSIS	expressed_in	concept	0.50
Coronary Artery Disease	inhibits	disease	0.50
Cellular Senescence	regulates	cell_type	0.50
DISEASE-ASSOCIATED MICROGLIA	interacts_with	concept	0.50
White Matter	activates	process	0.50
GRAY MATTER	activates	concept	0.50
GLIOSIS	associated_with	concept	0.50
Nlrp3 Inflammasome	activates	pathway	0.50
MONOCYTE	associated_with	concept	0.50
Pulmonary Fibrosis	associated_with	disease	0.50
MACROPHAGES	associated_with	concept	0.50
GENE EXPRESSION	regulates	concept	0.50
CARDIOVASCULAR DISEASE	activates	concept	0.50
Myocardial Infarction	associated_with	disease	0.50
HUNTINGTON'S	expressed_in	concept	0.50
Ovarian Cancer	associated_with	disease	0.50
METFORMIN	associated_with	concept	0.50
α-SYNUCLEIN	inhibits	concept	0.50
Cognitive Decline	causes	disease	0.50
NEURODEGENERATIVE DISEASE	inhibits	concept	0.50
NUCLEUS	causes	concept	0.50
Microbiota	activates	process	0.50
AKT1S1	activates	concept	0.50
DOPAMINERGIC	causes	concept	0.50
α-SYNUCLEIN	causes	concept	0.50

Incoming (1647)

Source	Relation	Type	Str
34616067	implicated as selectively vulnerable in	paper	0.90
34415665	is a risk factor for	paper	0.90
Abnormal Stress Granule Accumulation	contributes_to	phenotype	0.90
Redox Signaling	associated_with	process	0.88
Aberrant Condensates	causes	mechanism	0.85
m6A Modification	associated_with	process	0.85
Frailty	risk_factor_for	phenotype	0.85
Ferroptosis	associated_with	process	0.80
Ageing	increases_risk	process	0.80
SIRTUINS	implicated_in	protein	0.80
Excessive Cell Death	contributes_to	process	0.80
autophagy	protects_against	process	0.70
34616067	are selectively vulnerable in	paper	0.60
38923692	are important drivers of	paper	0.60
ATG16L1	activates	gene	0.50
PRMT1	implicated_in	gene	0.50
microglia	decreases_risk	cell_type	0.50
PRMT5	implicated_in	gene	0.50
IFN	implicated_in	gene	0.50
TAX1BP1	implicated_in	gene	0.50
EGR1	implicated_in	gene	0.50
G3BP1	implicated_in	gene	0.50
ALS	implicated_in	gene	0.50
GSS	implicated_in	gene	0.50
FUS	implicated_in	gene	0.50
NBR1	implicated_in	gene	0.50
IRF3	implicated_in	gene	0.50
TRIM21	implicated_in	gene	0.50
MAP1LC3	implicated_in	gene	0.50
NDP52	implicated_in	gene	0.50
BECN1	implicated_in	gene	0.50
EIF2Α	activates	protein	0.50
GFP	implicated_in	gene	0.50
ULK1	implicated_in	gene	0.50
SMCR8	implicated_in	gene	0.50
VCP	implicated_in	gene	0.50
mTOR	activates	entity	0.50
TOLLIP	implicated_in	gene	0.50
GABARAP	activates	protein	0.50
LC3	implicated_in	gene	0.50
CASP3	activates	gene	0.50
VPS34	activates	protein	0.50
SLC16A2	implicated_in	gene	0.50
NF-κB	activates	concept	0.50
Neuroinflammatory	activates	pathway	0.50
TREH	causes	gene	0.50
HSPB8	activates	gene	0.50
PPP3CB	activates	gene	0.50
DEMENTIA	associated_with	gene	0.50
SETX	inhibits	gene	0.50

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Closed-loop transcranial focused ultrasound targeting EC-II	0.958	Alzheimer's disease	Circuit-level neural dynamics in neurode
Closed-loop transcranial focused ultrasound to restore hippo	0.951	Alzheimer's disease	Circuit-level neural dynamics in neurode
Closed-loop transcranial focused ultrasound targeting EC-II	0.940	Alzheimer's disease	Circuit-level neural dynamics in neurode
Closed-loop transcranial focused ultrasound to restore hippo	0.912	Alzheimer's disease	Circuit-level neural dynamics in neurode
ACSL4-Driven Ferroptotic Priming in Disease-Associated Micro	0.869	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di

Optogenetic restoration of hippocampal gamma oscillations vi	0.865	Alzheimer's disease	Circuit-level neural dynamics in neurode
TREM2-Deficient Microglia as Drivers of Amyloid Plaque Toxic	0.827	neurodegeneration	Legacy Pre-Pipeline Hypothesis Import
Closed-loop transcranial focused ultrasound to restore hippo	0.827	Alzheimer's disease	Circuit-level neural dynamics in neurode
ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drive	0.801	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Pri	0.801	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
Closed-loop transcranial focused ultrasound targeting CA1 PV	0.797	Alzheimer's disease	Circuit-level neural dynamics in neurode
NMN Supplementation Restores SIRT1/p66Shc/FOXO3 Epigenetic A	0.790	neurodegeneration	epigenetic reprogramming aging neurons
Closed-loop tACS targeting entorhinal cortex layer II SST in	0.784	Alzheimer's disease	Circuit-level neural dynamics in neurode
LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferrop	0.779	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligo	0.779	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
Tissue-specific interactome destabilization drives phenotype	0.000	Mendelian neurological diseases (neurodegeneration)	What molecular mechanisms drive tissue-s
APOE4-driven loss of neuronal PI(4,5)P2 bridges ganglioside-	0.000	Alzheimer disease	Lipid metabolism dysregulation and membr
TFEB Activation to Restore Lysosomal Function in Parkinson's	0.000	proteomics	Quantitative proteomics of the aging syn
LXRβ-Selective Agonism Enhances CYP2J2-Mediated DHA Epoxide	0.000	lipidomics	Lipid metabolism dysregulation in Alzhei
ω-3 Docosahexaenoic Acid (DHA) Metabolism via 15-Lipoxygenas	0.000	lipidomics	Lipid metabolism dysregulation in Alzhei
Circulating hs-CRP as Disease-Modifying Target via Astrocyti	0.000	immunomics	Systemic immune profiling in neurodegene
TFEB Family Multi-Target Activation for Synaptic Lysosomal R	0.000	proteomics	Quantitative proteomics of the aging syn
Optogenetic restoration of SST interneuron-mediated dendriti	0.000	Alzheimer's disease	Circuit-level neural dynamics in neurode
Closed-loop transcranial focused ultrasound with adaptive AP	0.000	-	Survival Analysis of AD Patient Cohorts:
Circulating hs-CRP as Disease-Modifying Target via Astrocyti	0.000	immunomics	Systemic immune profiling in neurodegene
Closed-loop tFUS targeting of EC-II SST interneurons to prev	0.000	Alzheimer's disease	Circuit-level neural dynamics in neurode
ACSL4-Mediated Neuroinflammatory Amplification in Disease-As	0.000	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
TFEB Activation to Restore Lysosomal Biogenesis in Parkinson	0.000	proteomics	Quantitative proteomics of the aging syn
TFEB Activation to Restore Lysosomal Biogenesis in Alzheimer	0.000	proteomics	Quantitative proteomics of the aging syn
Mitochondrial Dysfunction-Mediated Neurodegeneration in Alzh	0.000	-	Survival Analysis of AD Patient Cohorts:

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (6)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Plant-based dietary patterns and Alzheimer's disease risk in multiethn	clinical	Alzheimer's disease and relate	0.950	0.00	human patients	proposed	N/A
SAHA@LIPO-ANG2 therapeutic efficacy in 5xFAD mice	validation	Alzheimer's disease	0.900	0.00	5xFAD transgenic mice	proposed	N/A
Transcriptomic profiling and differential expression analysis	exploratory	Alzheimer's disease	0.900	0.00	1-month-old APP/PS1 mice cereb	proposed	N/A
SIRPα modulation in mouse models of Alzheimer's disease	validation	Alzheimer's disease	0.900	0.00	mouse models of Alzheimer's di	proposed	N/A
Microglial SIRPα expression in human Alzheimer's disease tissue	exploratory	Alzheimer's disease	0.800	0.00	human brain tissue	proposed	N/A
Closed-loop tFUS Enhances Glymphatic Clearance and Restores CA1 PV Int	in_vivo	Alzheimer's disease	0.765	0.55	APP/PS1 mice 8-11 months (n=10	proposed	$125,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Transcriptomic cytoarchitecture reveals principles of human neocortex organizati [PMID:37824655]	Jorstad NL, Close J, Johansen N, Yanny A	Science	2023	186
FAK/SRC-JNK axis promotes ferroptosis via upregulating ACSL4 expression. [PMID:41862445]	Qin J, Ma S, Wang J, Huang S, Luan J, He	Cell death & disease	2026	0
Quercetin attenuates ox-LDL-induced endothelial injury by regulating ferroptosis [PMID:41902795]	Gao C, Liu B, Zhang R, Tian J, Xin H	Toxicology mechanisms and meth	2026	0
NEDD8 promotes the ferritinophagy and ferroptosis of neurons in ischemic stroke [PMID:41662890]	Rao W, Huang Y, Li J, Chen Q, Sun J et a	J Stroke Cerebrovasc Dis	2026	0
Inhibition of Ferroptosis in Prostatitis Model by Low Intensity Extracorporeal S [PMID:41714892]	Lin D, Li K, Kuang W, Chen Z, Zhang M	World J Mens Health	2026	0
Deciphering sorafenib resistance in hepatocellular carcinoma via ferroptotic mec [PMID:41763496]	Che L, Zhu L, Zhou L, Zhou Y	Biochim Biophys Acta Rev Cance	2026	0
B4GALT1 deficiency attenuates steatohepatitis by regulating the PPARγ/ACSL4 axis [PMID:41860570]	Chien Y, Xia R, Zhou D, Ai Y, Wu L et al	Hepatol Commun	2026	0
Unraveling the impact of risk factors on the ferroptosis-Alzheimer's disease lin [PMID:41498558]	Singh P, Rath SL	Journal of Alzheimer's disease	2026	0
Resveratrol Alleviates Intervertebral Disc Degeneration by Targeting NCOA4-Media [PMID:41873334]	Song C, Wu X, Chen C, Shen B, He Y, Liu	Drug design, development and t	2026	0
Pan-PPAR agonist bezafibrate alleviates psoriasis by suppressing LCN2-dependent [PMID:41662914]	["Xin R", "Zhang J", "Zhang Y", "Dai M",	Free radical biology & medicin	2026	0
Acteoside alleviates sepsis-induced acute lung injury by activating the Nrf2 pat [PMID:41895086]	Wang Y, Zhang W, Zhang M, Zhu Y, Wang W,	Tissue & cell	2026	0
Ferroptosis and microglial polarization in retinal vein occlusion: pathological [PMID:41924362]	Xu J, Sun M, Wang C, Ju P, Guan XD, Xie	International journal of ophth	2026	0
Retinal Müller glia alterations and their impact on ocular glymphatic clearance [PMID:41603340]	Das G, Raghunathan R, Wang L	J Alzheimers Dis	2026	0
Melatonin Alleviates Erastin-Induced Cell Death by Inhibiting Ferroptosis and Am [PMID:40442550]	Wongjaikam S, Siengdee P, Somnus A, Govi	Neurotoxicity research	2025	0
Acyl-CoA synthetase long-chain family member 4-A novel prognostic marker in cuta [PMID:41918944]	Paria S, Lapides R, Saravi B, Rajagopal	Frontiers in medicine	2025	0
The Glymphatic-Venous Axis in Brain Clearance Failure: Aquaporin-4 Dysfunction, [PMID:41226584]	["Costea D", "Dobrin N", "Tataru C", "To	International journal of molec	2025	0
Microglial exosome TREM2 ameliorates ferroptosis and neuroinflammation in alzhei [PMID:40640358]	Zhu L, Zhou T, Wu L, Zhu X, Chen L, Zhan	Scientific reports	2025	0
Microbiota-derived lysophosphatidylcholine alleviates Alzheimer's disease pathol [PMID:39510074]	["Zha Xu", "Liu Xicheng", "Wei Mengping"	Cell metabolism	2025	0
Upregulation of MAM by C99 disrupts ACSL4 activity and phospholipid homeostasis [PMID:41394684]	Montesinos J, Yun TD, Salomón-Cruz ID, A	bioRxiv : the preprint server	2025	0
Danggui Shaoyao San ameliorates Alzheimer's disease by regulating lipid metaboli [PMID:40271063]	Gong K, Zhou S, Xiao L, Xu M, Zhou Y, Lu	Frontiers in pharmacology	2025	0

Debates (0)

Multi-agent debates referencing this entity

No debates reference this entity

Related Research

Hypotheses and analyses mentioning DISEASE in their description or question text

Optogenetic restoration of hippocampal gamma oscillations via selective PV inter

Score: 0.865 · Alzheimer's disease · 2026-04-07

## Mechanistic Overview Optogenetic restoration of hippocampal gamma oscillations via selective PV interneuron activatio

TREM2-Deficient Microglia as Drivers of Amyloid Plaque Toxicity in Alzheimer's D

Score: 0.827 · neurodegeneration · 2026-04-26

TREM2 loss-of-function variants impair microglial survival, clustering around amyloid plaques, and phagocytic clearance,

Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscilla

Score: 0.827 · Alzheimer's disease · 2026-04-16

## Mechanistic Overview Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via glymph

ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drives White Matter Degen

Score: 0.801 · Alzheimer's Disease · 2026-04-05

## Mechanistic Overview ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drives White Matter Degeneration in Alzhe

40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively

Score: 0.801 · Alzheimer's Disease · 2026-04-05

## Mechanistic Overview 40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively Eliminate Diseas

Closed-loop transcranial focused ultrasound targeting CA1 PV interneurons with r

Score: 0.797 · Alzheimer's disease · 2026-04-07

## Mechanistic Overview Closed-loop transcranial focused ultrasound targeting CA1 PV interneurons with real-time gamma f

NMN Supplementation Restores SIRT1/p66Shc/FOXO3 Epigenetic Axis and Dopaminergic

Score: 0.790 · neurodegeneration · 2026-04-22

## Mechanistic Overview NMN Supplementation Restores SIRT1/p66Shc/FOXO3 Epigenetic Axis and Dopaminergic Neuron Survival

Closed-loop tACS targeting entorhinal cortex layer II SST interneurons to activa

Score: 0.784 · Alzheimer's disease · 2026-04-05

## Mechanistic Overview Closed-loop tACS targeting entorhinal cortex layer II SST interneurons to activate AMPK-autophag

LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferroptotic Priming Engine

Score: 0.779 · Alzheimer's Disease · 2026-04-05

## Mechanistic Overview LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferroptotic Priming Engine in Disease-Asso

ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligodendrocytes Underlie

Score: 0.779 · Alzheimer's Disease · 2026-04-05

## Mechanistic Overview ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligodendrocytes Underlies White Matter D

Tissue-specific interactome destabilization drives phenotype divergence in Mende

Score: 0.000 · Mendelian neurological diseases (neurodegeneration) · 2026-04-26

Disease-causing mutations in shared genes produce tissue-specific phenotypes because the mutant protein exhibits differe

APOE4-driven loss of neuronal PI(4,5)P2 bridges ganglioside-mediated amyloid nuc

Score: 0.000 · Alzheimer disease · 2026-04-27

In APOE4 carriers, the composition of astrocyte-secreted APOE-containing lipid particles becomes enriched in ganglioside

TFEB Activation to Restore Lysosomal Function in Parkinson's Disease Alpha-Synuc

Score: 0.000 · proteomics · 2026-04-27

Parkinson's disease is characterized by the accumulation of misfolded alpha-synuclein protein aggregates (Lewy bodies) i

LXRβ-Selective Agonism Enhances CYP2J2-Mediated DHA Epoxide Generation to Restor

Score: 0.000 · lipidomics · 2026-04-27

This hypothesis proposes that LXRβ-selective agonists enhance CYP2J2 expression and activity to increase protective DHA

ω-3 Docosahexaenoic Acid (DHA) Metabolism via 15-Lipoxygenase to Generate Specia

Score: 0.000 · lipidomics · 2026-04-26

This hypothesis proposes that 15-lipoxygenase (15-LOX) enzymatically converts docosahexaenoic acid (DHA) into specialize