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.

2312Connections

30Hypotheses

0Analyses

50Outgoing

50Incoming

16Experiments

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
Pathological Protein Aggregation	associated_with	mechanism	0.95
Dna Defects	associated_with	mechanism	0.95
Rna Defects	associated_with	mechanism	0.95
Aberrant Proteostasis	associated_with	mechanism	0.95
Synaptic Dysfunction	associated_with	mechanism	0.95
Cytoskeletal Abnormalities	associated_with	mechanism	0.95
Organ Dysfunction	causes	phenotype	0.95
Altered Energy Homeostasis	associated_with	mechanism	0.95
Neuronal Network Dysfunction	associated_with	mechanism	0.95
Dendritic Cell	activates	cell_type	0.50
SEROTONIN	regulates	concept	0.50
PERICYTE	activates	cell_type	0.50
SEROTONIN	associated_with	concept	0.50
CYP1A1	activates	concept	0.50
CURCUMIN	regulates	concept	0.50
Cystic Fibrosis	activates	disease	0.50
DISEASE-ASSOCIATED MICROGLIA	activates	concept	0.50
SELECTIVE AUTOPHAGY	activates	concept	0.50
PPP3	activates	concept	0.50
NUCLEUS	associated_with	concept	0.50
PIKFYVE	inhibits	concept	0.50
MACROPHAGES	interacts_with	concept	0.50
AMYLOID-β	interacts_with	concept	0.50
ALZHEIMER'S	regulates	concept	0.50
RAPAMYCIN	activates	concept	0.50
SEROTONIN	activates	concept	0.50
Inflammatory Bowel Disease	activates	disease	0.50
CYTOKINE	activates	concept	0.50
TREHALOSE	activates	concept	0.50
TREHALOSE	causes	concept	0.50
Chronic Kidney Disease	activates	disease	0.50
Microrna	activates	pathway	0.50
Myocardial Infarction	activates	disease	0.50
Type 2 Diabetes	associated_with	disease	0.50
INSULIN	associated_with	concept	0.50
Retinopathy	activates	disease	0.50
cGAS-STING pathway	activates	pathway	0.50
MOTOR NEURON	inhibits	concept	0.50
PERICYTE	associated_with	cell_type	0.50
Neuroblastoma	activates	disease	0.50
COLORECTAL CANCER	activates	disease	0.50
STEM CELLS	activates	concept	0.50
DNA DAMAGE	activates	concept	0.50
NEURONS	inhibits	concept	0.50
NEURODEGENERATIVE DISEASE	interacts_with	concept	0.50
SYNUCLEIN	interacts_with	concept	0.50
Crohn Disease	activates	disease	0.50
α-SYNUCLEIN	interacts_with	concept	0.50
NEURODEGENERATIVE DISEASE	activates	concept	0.50
AKT1S1	activates	concept	0.50

Incoming (1649)

Source	Relation	Type	Str
34415665	is a risk factor for	paper	0.90
Abnormal Stress Granule Accumulation	contributes_to	phenotype	0.90
34616067	implicated as selectively vulnerable in	paper	0.90
Redox Signaling	associated_with	process	0.88
m6A Modification	associated_with	process	0.85
Frailty	risk_factor_for	phenotype	0.85
Aberrant Condensates	causes	mechanism	0.85
Excessive Cell Death	contributes_to	process	0.80
SIRTUINS	implicated_in	protein	0.80
Ageing	increases_risk	process	0.80
Ferroptosis	associated_with	process	0.80
autophagy	protects_against	process	0.70
22312439	may modify risk for	paper	0.60
24974230	may cause	paper	0.60
38923692	are important drivers of	paper	0.60
34616067	are selectively vulnerable in	paper	0.60
CFTR	activates	gene	0.50
NADH	implicated_in	gene	0.50
CGAS	activates	protein	0.50
ATG16L1	activates	gene	0.50
IDH1	implicated_in	gene	0.50
ACTB	implicated_in	gene	0.50
ATF6	activates	gene	0.50
CTSD	implicated_in	gene	0.50
ATG	implicated_in	gene	0.50
SREBF1	implicated_in	gene	0.50
GSS	implicated_in	gene	0.50
PPARG	implicated_in	gene	0.50
RPS6KB1	implicated_in	gene	0.50
PPARA	implicated_in	gene	0.50
LRP2	implicated_in	gene	0.50
HCN2	implicated_in	gene	0.50
RAB7A	implicated_in	gene	0.50
CD2AP	implicated_in	gene	0.50
CAT	implicated_in	gene	0.50
LRRK2	activates	gene	0.50
AKT1	activates	gene	0.50
SQSTM1	implicated_in	gene	0.50
ATP	implicated_in	gene	0.50
ROS	implicated_in	gene	0.50
Epithelial Cell	activates	cell_type	0.50
HCN4	implicated_in	gene	0.50
PIK3C3	implicated_in	gene	0.50
HCN1	implicated_in	gene	0.50
IDH2	implicated_in	gene	0.50
NAD	implicated_in	gene	0.50
RPS6	implicated_in	gene	0.50
MCU	implicated_in	gene	0.50
LETM1	implicated_in	gene	0.50
CDH1	activates	concept	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	0.968	alzheimers	Circuit-level neural dynamics in neurode
Closed-loop transcranial focused ultrasound targeting EC-II	0.955	alzheimers	Circuit-level neural dynamics in neurode
Closed-loop transcranial focused ultrasound to restore hippo	0.912	alzheimers	Circuit-level neural dynamics in neurode
ACSL4-Driven Ferroptotic Priming in Disease-Associated Micro	0.891	alzheimers	Cell type vulnerability in Alzheimers Di
Closed-loop transcranial focused ultrasound to restore hippo	0.865	alzheimers	Circuit-level neural dynamics in neurode

Optogenetic restoration of hippocampal gamma oscillations vi	0.865	alzheimers	Circuit-level neural dynamics in neurode
TREM2-Deficient Microglia as Drivers of Amyloid Plaque Toxic	0.847	neurodegeneration	Legacy Pre-Pipeline Hypothesis Import
Closed-loop transcranial focused ultrasound to restore hippo	0.827	alzheimers	Circuit-level neural dynamics in neurode
MAPT tau seeding and release across AD, FTD, and PD-spectrum	0.812	multi	Cross-disease neurodegeneration mechanis
ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drive	0.801	alzheimers	Cell type vulnerability in Alzheimers Di
40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Pri	0.801	alzheimers	Cell type vulnerability in Alzheimers Di
Closed-loop transcranial focused ultrasound targeting CA1 PV	0.797	alzheimers	Circuit-level neural dynamics in neurode
LRRK2 G2019S Kinase Inhibition for Parkinson's Disease	0.795	neurodegeneration	Test
HDAC6 Inhibition for Charcot-Marie-Tooth Disease and ALS	0.793	neurodegeneration	Test
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	alzheimers	Circuit-level neural dynamics in neurode
ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligo	0.779	alzheimers	Cell type vulnerability in Alzheimers Di
LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferrop	0.777	alzheimers	Cell type vulnerability in Alzheimers Di
LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Sub	0.776	alzheimers	Cell type vulnerability in Alzheimers Di
Complement C1q-Mediated Synaptic Pruning Drives Early Cognit	0.769	neurodegeneration	Legacy Pre-Pipeline Hypothesis Import
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	alzheimers	Circuit-level neural dynamics in neurode
LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Vul	0.764	alzheimers	Cell type vulnerability in Alzheimers Di
GBA1/GCase restoration to reduce alpha-synuclein pathology i	0.760	neurodegeneration	Test
TDP-43 Proteinopathy as a Cross-Disease Pathological Substra	0.760	neurodegeneration	Cross-disease neurodegeneration mechanis
C1QA/C1QB Subunit-Specific Inhibition to Block Aberrant PV I	0.747	neurodegeneration	Are interneuron oscillation deficits com
LAMP2A-Mediated Autophagy Enhancement Blocks Alpha-Synuclein	0.745	neurodegeneration	Test
LAMP2A Upregulation to Enhance Chaperone-Mediated Autophagy	0.000	proteomics	Quantitative proteomics of the aging syn
Closed-loop transcranial focused ultrasound to restore hippo	0.000	alzheimers	Circuit-level neural dynamics in neurode
Cell-Type-Specific TFEB Modulation Combined with Trehalose f	0.000	proteomics	Quantitative proteomics of the aging syn

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (16)

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	abandoned	$125,000
Single nuclei transcriptomic and epigenomic profiling of 84 donors acr	gene_expression	Alzheimer's disease	0.500	0.00	human	extracted	N/A
The Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD) integrates n	neuropathology	Alzheimer's disease	0.500	0.00	human	extracted	N/A
In late life, NfL demonstrated the strongest association with incident	clinical	Alzheimer's disease	0.500	0.00	human	extracted	N/A
Complex gene expression differences were identified, ranging from glob	gene_expression	Alzheimer's disease	0.500	0.00	post_mortem_brain	extracted	N/A
A subset of donors with particularly severe cellular and molecular phe	clinical	Alzheimer's disease	0.500	0.00	human	extracted	N/A
Midlife hypertension was associated with 0.15-SD faster NfL increase a	clinical	Alzheimer's disease	0.500	0.00	human	extracted	N/A
A subset of donors exhibited particularly severe cellular and molecula	computational	Alzheimer's disease	0.500	0.00	human	extracted	N/A
Cell type-specific analysis identified early-phase loss of somatostati	gene_expression	Alzheimer's disease	0.500	0.00	human	extracted	N/A
Single-cell/multiomics analysis of 84 human post-mortem brains reveale	computational	Alzheimer's disease	0.500	0.00	human	extracted	N/A
Temporal analysis of gene expression differences across disease progre	gene_expression	Alzheimer's disease	0.500	0.00	human	extracted	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
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 · alzheimers · 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: 0.847 · 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 · alzheimers · 2026-04-16

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

MAPT tau seeding and release across AD, FTD, and PD-spectrum disease

Score: 0.812 · multi · 2026-04-28

Shared mechanism across AD, FTD, PD: MAPT dysfunction creates a tau species that can detach from microtubules, aggregate

ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drives White Matter Degen

Score: 0.801 · alzheimers · 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 · alzheimers · 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 · alzheimers · 2026-04-07

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

LRRK2 G2019S Kinase Inhibition for Parkinson's Disease

Score: 0.795 · neurodegeneration · 2026-05-06

LRRK2 G2019S mutation hyperactivates kinase activity, causing excessive phosphorylation of Rab GTPases (Rab8A, Rab10, Ra

HDAC6 Inhibition for Charcot-Marie-Tooth Disease and ALS

Score: 0.793 · neurodegeneration · 2026-05-06

HDAC6 deacetylates α-tubulin and regulates cytoskeletal dynamics. HDAC6 overexpression causes axonal transport defects.

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 · alzheimers · 2026-04-05

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

ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligodendrocytes Underlie

Score: 0.779 · alzheimers · 2026-04-05

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

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

Score: 0.777 · alzheimers · 2026-04-05

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

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

Score: 0.776 · alzheimers · 2026-04-05

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

Complement C1q-Mediated Synaptic Pruning Drives Early Cognitive Decline in Alzhe

Score: 0.769 · neurodegeneration · 2026-04-26

C1q (classical complement cascade initiator) is upregulated in AD brain and tags synapses for microglial phagocytosis vi