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.

2307Connections

30Hypotheses

0Analyses

50Outgoing

50Incoming

5Experiments

0Debates

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💡 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
Aberrant Proteostasis	associated_with	mechanism	0.95
Neuronal Network Dysfunction	associated_with	mechanism	0.95
Dna Defects	associated_with	mechanism	0.95
Synaptic Dysfunction	associated_with	mechanism	0.95
Pathological Protein Aggregation	associated_with	mechanism	0.95
Altered Energy Homeostasis	associated_with	mechanism	0.95
Cytoskeletal Abnormalities	associated_with	mechanism	0.95
Rna Defects	associated_with	mechanism	0.95
CYTOKINE	activates	concept	0.50
NEURODEGENERATIVE DISEASE	interacts_with	concept	0.50
SEROTONIN	associated_with	concept	0.50
AMYLOID-β	interacts_with	concept	0.50
NEURODEGENERATIVE DISEASE	activates	concept	0.50
TREHALOSE	causes	concept	0.50
RAPAMYCIN	activates	concept	0.50
PIKFYVE	inhibits	concept	0.50
GSK3	activates	concept	0.50
SELECTIVE AUTOPHAGY	activates	concept	0.50
Inflammatory Bowel Disease	activates	disease	0.50
STEM CELLS	activates	concept	0.50
FRONTOTEMPORAL	associated_with	concept	0.50
NEURODEGENERATIVE DISEASE	causes	concept	0.50
α-SYNUCLEIN	associated_with	concept	0.50
SYNUCLEIN	interacts_with	concept	0.50
Neuroblastoma	activates	disease	0.50
α-SYNUCLEIN	interacts_with	concept	0.50
Reactive Oxygen Species	inhibits	process	0.50
Asthma	associated_with	disease	0.50
GENE EXPRESSION	expressed_in	concept	0.50
Asthma	expressed_in	disease	0.50
PPP3	activates	concept	0.50
Fatty Liver	inhibits	disease	0.50
CARDIOVASCULAR DISEASE	interacts_with	concept	0.50
CARDIOVASCULAR DISEASE	associated_with	concept	0.50
Osteoporosis	associated_with	disease	0.50
PARKINSON'S	regulates	concept	0.50
Immunotherapy	associated_with	process	0.50
CENTRAL NERVOUS SYSTEM	associated_with	concept	0.50
Retinopathy	activates	disease	0.50
CHAPERONE-MEDIATED AUTOPHAGY	activates	concept	0.50
CEREBROSPINAL FLUID	interacts_with	concept	0.50
Protein Aggregation	associated_with	process	0.50
Chronic Kidney Disease	activates	disease	0.50
ALS-CAUSING MUTATIONS	inhibits	concept	0.50
IPSC	activates	concept	0.50
SYNUCLEIN	associated_with	concept	0.50
Microrna	activates	pathway	0.50
PARKINSON'S	inhibits	concept	0.50
DMSO	activates	concept	0.50

Incoming (1644)

Source	Relation	Type	Str
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
Frailty	risk_factor_for	phenotype	0.85
m6A Modification	associated_with	process	0.85
Aberrant Condensates	causes	mechanism	0.85
Excessive Cell Death	contributes_to	process	0.80
Ferroptosis	associated_with	process	0.80
SIRTUINS	implicated_in	protein	0.80
Ageing	increases_risk	biological_process	0.80
autophagy	protects_against	process	0.70
RETREG1	activates	concept	0.50
CELL CYCLE	activates	cell_type	0.50
cancer	activates	disease	0.50
RIP3	activates	concept	0.50
PGAM5	activates	concept	0.50
AMPK	activates	protein	0.50
PARKINSON	activates	gene	0.50
Neurodegenerative Diseases	associated_with	disease	0.50
EIF2S1	activates	concept	0.50
MICROTUBULES	associated_with	concept	0.50
Neuron	associated_with	cell_type	0.50
PPAR	activates	protein	0.50
ALZHEIMER	associated_with	gene	0.50
Alzheimer'S Disease	associated_with	disease	0.50
ALZHEIMER	inhibits	gene	0.50
Alzheimer'S Disease	inhibits	disease	0.50
AMYLOID	inhibits	gene	0.50
CD2AP	interacts_with	protein	0.50
ALZHEIMER	interacts_with	gene	0.50
Autophagy	interacts_with	process	0.50
HIF1	activates	concept	0.50
DEMENTIA	activates	gene	0.50
REELIN	interacts_with	protein	0.50
Neuropathy	associated_with	disease	0.50
SCHIZOPHRENIA	interacts_with	disease	0.50
lissencephaly	interacts_with	disease	0.50
Alzheimer'S Disease	interacts_with	disease	0.50
PARKINSON	interacts_with	gene	0.50
Parkinson's Disease	interacts_with	disease	0.50
Neurodegenerative Diseases	interacts_with	disease	0.50
Cardiac	associated_with	disease	0.50
cancer	interacts_with	disease	0.50
Neurodegeneration	associated_with	disease	0.50
STROKE	associated_with	gene	0.50
cancer	associated_with	disease	0.50
DIABETES	associated_with	disease	0.50
Heart Failure	associated_with	disease	0.50
microglia	causes	cell_type	0.50
Parkinson's Disease	associated_with	disease	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	0.948	Alzheimer's disease	Circuit-level neural dynamics in neurode
Closed-loop transcranial focused ultrasound targeting EC-II	0.922	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
Optogenetic restoration of hippocampal gamma oscillations vi	0.863	Alzheimer's disease	Circuit-level neural dynamics in neurode
Closed-loop transcranial focused ultrasound to restore hippo	0.858	Alzheimer's disease	Circuit-level neural dynamics in neurode

ACSL4-Driven Ferroptotic Priming in Disease-Associated Micro	0.847	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
Optogenetic viral vector delivery via tFUS-mediated blood-br	0.846	Alzheimer's disease	Circuit-level neural dynamics in neurode
Optogenetic restoration of hippocampal gamma oscillations vi	0.845	Alzheimer's disease	Circuit-level neural dynamics in neurode
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
LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Sub	0.776	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Vul	0.770	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
Oligodendrocyte Precursor Cell Senescence in White Matter Di	0.769	-	Senescent cell clearance as neurodegener
Closed-loop transcranial focused ultrasound to restore hippo	0.767	Alzheimer's disease	Circuit-level neural dynamics in neurode
C1QA/C1QB Subunit-Specific Inhibition to Block Aberrant PV I	0.747	neurodegeneration	Are interneuron oscillation deficits com
VPS35 retromer activation prevents endosomal tau templating	0.740	neurodegeneration	Which tau propagation mechanism predomin
Context-Dependent Cx43 Modulation Based on Disease Stage	0.724	cell biology	What is the relative contribution of con
Excessive C1q/C3/CR3 complement cascade activation initiates	0.720	neurodegeneration	Synaptic pruning by microglia in neurode
Disease-Associated Microglia Metabolic Reprogramming	0.718	neurodegeneration	Cell type vulnerability in Alzheimers Di
Regional TREM2-Dependent Lipid Metabolism Determines Cortica	0.710	neuroinflammation	How do regional, age, and sex-dependent
Microglial Disease-Associated States: TREM2-Independent Path	0.710	neurodegeneration	Cell type vulnerability debate in Alzhei
TREM2 haploinsufficiency dysregulates microglial synaptic su	0.700	neurodegeneration	Synaptic pruning by microglia in neurode
TREM2-Dependent Microglial State Transition as Therapeutic W	0.690	neurodegeneration	Gap 006 analysis (archived stub)
Microglial TREM2 downregulation impairs damage-associated re	0.628	Alzheimer's disease	SEA-AD Single-Cell Analysis: Cell-Type V

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (5)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
Plant-based dietary patterns and Alzheimer's disease risk in multiethn	clinical	Alzheimer's disease and relate	0.950	human patients	proposed	N/A
SIRPα modulation in mouse models of Alzheimer's disease	validation	Alzheimer's disease	0.900	mouse models of Alzheimer's di	proposed	N/A
SAHA@LIPO-ANG2 therapeutic efficacy in 5xFAD mice	validation	Alzheimer's disease	0.900	5xFAD transgenic mice	proposed	N/A
Transcriptomic profiling and differential expression analysis	exploratory	Alzheimer's disease	0.900	1-month-old APP/PS1 mice cereb	proposed	N/A
Microglial SIRPα expression in human Alzheimer's disease tissue	exploratory	Alzheimer's disease	0.800	human brain tissue	proposed	N/A

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
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
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
Single-cell spatial transcriptomics reveals distinct patterns of dysregulation i [PMID:39103533]	Johnston KG, Berackey BT, Tran KM, Gelbe	Molecular psychiatry	2025	0
Deferiprone in Alzheimer Disease: A Randomized Clinical Trial. [PMID:39495531]	Ayton S, Barton D, Brew B, Brodtmann A,	JAMA neurology	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

ACSL4-Driven Ferroptotic Priming in Disease-Associated Microglia

Score: 0.847 · Alzheimer's Disease · 2026-04-02

## Mechanistic Overview ACSL4-Driven Ferroptotic Priming in Disease-Associated Microglia starts from the claim that modu

Optogenetic viral vector delivery via tFUS-mediated blood-brain barrier opening

Score: 0.846 · Alzheimer's disease · 2026-04-07

## Mechanistic Overview Optogenetic viral vector delivery via tFUS-mediated blood-brain barrier opening to restore hippo

Optogenetic restoration of hippocampal gamma oscillations via selective SST inte

Score: 0.845 · Alzheimer's disease · 2026-04-07

## Mechanistic Overview Optogenetic restoration of hippocampal gamma oscillations via selective SST interneuron activati

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

LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Substrate Pools in Dise

Score: 0.776 · Alzheimer's Disease · 2026-04-05

## Mechanistic Overview LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Substrate Pools in Disease-Associated M

LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Vulnerability in Diseas

Score: 0.770 · Alzheimer's Disease · 2026-04-05

## Mechanistic Overview LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Vulnerability in Disease-Associated Mic

Oligodendrocyte Precursor Cell Senescence in White Matter Disease

Score: 0.769 · unknown disease · 2026-04-16

## Mechanistic Overview Oligodendrocyte Precursor Cell Senescence in White Matter Disease starts from the claim that mod

Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscilla

Score: 0.767 · Alzheimer's disease · 2026-04-12

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