concept

IR

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about IR: 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.

74Connections

30Hypotheses

0Analyses

48Outgoing

26Incoming

19Experiments

0Debates

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💡 Concept Info

Name	IR
Key Genes/Proteins	AKT, ALOX12, AMPK, ANGPT1, ATM, BACE1
Related Diseases	Alzheimer's disease, diabetes
Related Pathways	apoptosis pathway, blood-brain barrier
Linked Hypotheses	24 hypotheses

Wiki Pages (20)

Knowledge base pages for this entity

Pathway Diagram

graph TD
    IR[IR]
    IR -->|activates| neuroinflammation[neuroinflammation]
    IR -->|expressed in| macrophages[macrophages]
    IR -->|activates| PI3K[PI3K]
    IR -->|activates| neurodegeneration[neurodegeneration]
    IR -->|interacts| MAP2[MAP2]
    IR -->|activates| NLRP3[NLRP3]
    IR -->|activates| TNF[TNF]
    IR -->|activates| stroke[stroke]
    IR -->|activates| MET[MET]
    DNA[DNA] -->|inhibits| IR
    AKT[AKT] -->|activates| IR
    GFAP[GFAP] -->|implicated in| IR
    BACE1[BACE1] -->|activates| IR
    CERS2[CERS2] -->|activates| IR
    ALOX12[ALOX12] -->|implicated in| IR
    ANGPT1[ANGPT1] -->|activates| IR
    HDAC3[HDAC3] -->|activates| IR

Outgoing (48)

Target	Relation	Type	Str
benchmark_ot_ad_answer_key:IR	data_in	dataset_row	0.00
neuroinflammation	activates	disease	0.70
macrophages	expressed_in	cell_type	0.70
PI3K-AKT-mTOR signaling	participates_in	pathway	0.60
LDL	associated_with	gene	0.60
synaptic plasticity	participates_in	pathway	0.60
diabetes	protects_against	disease	0.60
PINK	activates	gene	0.60
pyroptosis	participates_in	pathway	0.60
Alzheimer's disease	activates	disease	0.60
apoptosis pathway	participates_in	pathway	0.60
senescence	participates_in	pathway	0.60
Alzheimer's disease	associated_with	disease	0.60
oxidative stress response	participates_in	pathway	0.60
diabetes	activates	disease	0.60
PARP1	inhibits	gene	0.60
RAD51	inhibits	gene	0.60
diabetes	associated_with	disease	0.60
TGF	interacts_with	gene	0.60
TGF-beta signaling	participates_in	pathway	0.60
ubiquitin-proteasome	participates_in	pathway	0.60
blood-brain barrier	participates_in	pathway	0.60
MAPK signaling	participates_in	pathway	0.60
RNA	interacts_with	gene	0.60
neurodegeneration	associated_with	disease	0.60
PI3K	activates	gene	0.60
neurodegeneration	activates	disease	0.60
MAP2	interacts_with	gene	0.60
NLRP3	activates	gene	0.60
TNF	activates	gene	0.60
stroke	activates	disease	0.60
MET	activates	gene	0.60
MET	biomarker_for	gene	0.60
PSEN1	regulates	gene	0.60
neurodegeneration	interacts_with	disease	0.60
neuroinflammation	interacts_with	disease	0.60
neuroinflammation	associated_with	disease	0.60
ferroptosis	participates_in	pathway	0.60
TGM2	inhibits	gene	0.60
neurodegeneration	inhibits	disease	0.60
LRP2	targets	gene	0.60
LRP2	regulates	gene	0.60
TH	expressed_in	gene	0.60
JNK	activates	gene	0.60
NBS1	inhibits	gene	0.60
astrocytes	expressed_in	cell_type	0.55
microglia	expressed_in	cell_type	0.55
neurons	expressed_in	cell_type	0.55

Incoming (26)

Source	Relation	Type	Str
benchmark_ot_ad_answer_key:IR	data_in	dataset_row	0.00
DNA	inhibits	gene	0.70
CLCN1	associated_with	gene	0.70
CP	associated_with	gene	0.60
ALOX12	associated_with	gene	0.60
ANGPT1	activates	gene	0.60
HDAC3	activates	gene	0.60
CERS2	activates	gene	0.60
HDAC3	associated_with	gene	0.60
HDAC3	inhibits	gene	0.60
rapamycin	targets	drug	0.60
DNA	interacts_with	gene	0.60
HDAC3	protects_against	gene	0.60
AKT	activates	gene	0.60
BACE1	activates	gene	0.60
INS	biomarker_for	gene	0.60
AMPK	activates	gene	0.60
DNA	implicated_in	gene	0.60
GFAP	interacts_with	gene	0.60
H2AX	activates	gene	0.60
H2AX	associated_with	gene	0.60
GFAP	implicated_in	gene	0.60
HIF	activates	gene	0.60
metformin	targets	drug	0.60
DNA	activates	gene	0.60
ATM	inhibits	gene	0.60

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Nutrient-Sensing Epigenetic Circuit Reactivation	0.907	neurodegeneration	Epigenetic reprogramming in aging neuron
SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senesc	0.895	neurodegeneration	Gene expression changes in aging mouse b
Multi-Target Hypothesis: Aβ-Induced Cholinergic Damage is Pa	0.887	-	Do β-amyloid plaques and neurofibrillary
H1: TREM2 Agonism to Redirect APOE4-Enhanced Microglia from	0.887	neurodegeneration	How does APOE4's beneficial immune funct
Closed-loop transcranial focused ultrasound to restore hippo	0.858	Alzheimer's disease	Circuit-level neural dynamics in neurode

Closed-loop tACS targeting EC-II PV interneurons to suppress	0.857	Alzheimer's disease	Circuit-level neural dynamics in neurode
Optogenetic viral vector delivery via tFUS-mediated blood-br	0.846	Alzheimer's disease	Circuit-level neural dynamics in neurode
miR-155/Interferon-gamma Feedback Loop as a Reversible Molec	0.843	neurodegeneration	How do different microglial subtypes (DA
Circadian Glymphatic Entrainment via Targeted Orexin Recepto	0.841	neurodegeneration	Perivascular spaces and glymphatic clear
Sequential Iron Chelation (Deferoxamine) and GPX4 Restoratio	0.838	neurodegeneration	View
SIRT1 Activation Couples Mitochondrial Biogenesis to Ferropt	0.824	neurodegeneration	View
Hippocampal CA3-CA1 circuit rescue via neurogenesis and syna	0.820	Alzheimer's disease	Circuit-level neural dynamics in neurode
NMN Supplementation Restores SIRT1/p66Shc/FOXO3 Epigenetic A	0.790	neurodegeneration	epigenetic reprogramming aging neurons
SIRT1/PGC-1α Axis Activation to Preserve Mitochondrial Resil	0.778	neurodegeneration	How do gut microbiome-derived metabolite
Prefrontal sensory gating circuit restoration via PV interne	0.775	Alzheimer's disease	Circuit-level neural dynamics in neurode
Alpha-gamma cross-frequency coupling enhancement to restore	0.775	Alzheimer's disease	Circuit-level neural dynamics in neurode
H3: SIRT1 Insufficiency Disconnects Metabolic Sensing from E	0.770	neurodegeneration	Investigate mechanisms of epigenetic rep
Direct Toxicity Hypothesis: β-Amyloid Directly Impairs Choli	0.769	-	Do β-amyloid plaques and neurofibrillary
Circadian Clock-Autophagy Synchronization	0.763	neurodegeneration	Sleep disruption as cause and consequenc
APOE4 astrocytes exhibit impaired cholesterol efflux via ABC	0.760	neuroscience	APOE4-driven lipid metabolism dysregulat
Dual-Circuit Tau Vulnerability Cascade	0.754	neuroscience	Circuit-level neural dynamics in neurode
METTL3-Mediated m6A Modification of lncRNA-0021 Regulates mi	0.754	molecular neurobiology	View
Iron-driven lipid peroxidation and GPX4 failure create a fer	0.750	neurodegeneration	What mechanisms drive the self-amplifyin
Circadian-Synchronized Proteostasis Enhancement	0.744	neurodegeneration	Digital biomarkers and AI-driven early d
TREM2-SIRT1 Metabolic Senescence Circuit in Microglial Aging	0.744	neurodegeneration	Gene expression changes in aging mouse b
Cholinergic Basal Forebrain-Hippocampal Circuit Protection	0.742	neuroscience	Circuit-level neural dynamics in neurode
miR-33 Antisense Oligonucleotide Hyper-Lipidation Strategy	0.741	molecular biology	Is APOE4's reduced lipid binding pathoge
Kinetic Modeling Predicts Threshold-Dependent Efficacy—Early	0.740	protein folding	Can chaperone enhancement approaches ove
Dopaminergic Ventral Tegmental-Hippocampal Circuit Protectio	0.740	neuroscience	Circuit-level neural dynamics in neurode
SIRT3-Mediated Mitochondrial Deacetylation Failure with PINK	0.738	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (19)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Gandouling protection against brain injury in Wilson's disease via SIR	validation	Hepatolenticular degeneration	0.900	0.00	TX mice (Wilson's disease mode	proposed	N/A
CSF Dynamic Biomarkers for Differential Diagnosis of NPH vs AD with Co	clinical	Alzheimer's Disease	0.900	0.50	aortic endothelial cells	proposed	$6,550,000
Microglial SIRPα expression in human Alzheimer's disease tissue	exploratory	Alzheimer's disease	0.800	0.00	human brain tissue	proposed	N/A
Cognitive Reserve Mechanisms in Alzheimer's Disease — Molecular Basis	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$6,550,000
Epigenetic Clocks in Neurodegeneration — Causal Drivers or Passive Mar	validation	Neurodegeneration	0.400	0.50	human	proposed	$3,000,000
Epigenetic Dysregulation Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$7,500,000
Lifestyle Intervention Mechanisms in Alzheimer's Disease	validation	Alzheimer's Disease	0.400	0.50	mouse	proposed	$430,000
Normal Aging to Alzheimer's Disease Transition Trigger — Identifying t	validation	Alzheimer's Disease	0.400	0.50	human	proposed	$2,280,000
Sirtuin Dysfunction Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Sirtuin Pathway Dysfunction Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
s:** - Test tau spreading in AQP4 knockout vs wild-type mice with PSP/	falsification	Neurodegeneration	0.400	0.50	mouse	proposed	$260,000
Circadian-Vascular-Metabolic Syndrome (CVMS) Intervention Trial	clinical	Neurodegeneration	0.400	0.50	human	proposed	$3,900,000
DLB Cognitive Fluctuation Mechanism Experiment	clinical	Neurodegeneration	0.400	0.50	human	proposed	$6,550,000
Glymphatic-Circadian Axis Enhancement Therapy for Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
Non-Motor Symptom Progression in Parkinson's Disease — Mechanisms and	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
NPH Glymphatic System Interaction Experiment	clinical	Neurodegeneration	0.400	0.50	human	proposed	$5,460,000
Sleep and Circadian Dysfunction as Driver of Neurodegeneration	clinical	Neurodegeneration	0.400	0.50	human	proposed	$5,460,000
Sleep Disruption and Alzheimer's Disease — mechanism and intervention	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
Sleep and Respiratory Network Interaction in ALS — Experiment Design	clinical	ALS	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
Combined effects of HCRTR1/2 gene variants and non-genetic factors on sleep-wake [PMID:40439868]	Zheng Z, Xue F, Wang H, Gu Q, Hu R, Li X	Pharmacol Rep	2025	1
Genetic determinants of daytime napping and effects on cardiometabolic health. [PMID:33568662]	Dashti HS, Daghlas I, Lane JM, Huang Y,	Nat Commun	2021	1
Hypocretin/Orexin Receptor Pharmacology and Sleep Phases. [PMID:34052813]	Sun Y, Tisdale RK, Kilduff TS	Front Neurol Neurosci	2021	1
Sleep drives metabolite clearance from the adult brain. [PMID:24136970]	Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Th	Science	2013	1
NAD+ subcellular partitioning mediated by miR-183 and miR-96 regulates muscle st [PMID:41915008]	Ma M, Ma R, Li Z, Shen S, Kong W, Qiu T,	Journal of molecular cell biol	2026	0
Rhodiola sacra Protects Against Hippocampal Neuronal Apoptosis in Chronic Cerebr [PMID:41879438]	Zhou L, Jia J, Li J, Yao Z, Fu Z, Wang S	Current neuropharmacology	2026	0
Mechanistic Modulation of Autophagy by Bioactive Natural Products: Implications [PMID:41830033]	Jalouli M, Harrath AH, Al-Zharani M, Rah	Nutrients	2026	0
Changes in Circulating Levels of miR-30b During Minipuberty and Puberty in Girls [PMID:40899010]	Albrechtsen HM, Saritas G, Winge SB, Mai	J Clin Endocrinol Metab	2026	0
Epigenetics in chronic rhinosinusitis. [PMID:41442742]	Kumar N, Brar T, Lal D	Curr Opin Otolaryngol Head Nec	2026	0
Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in [PMID:41645754]	Li W, Wang WH, Song Y, Li XJ, Li Y et al	Int J Mol Med	2026	0
Extracellular vesicles in type 2 diabetes exhibit elevated miR-155 cargo and Ann [PMID:41786286]	Jackson G, Islam H, de Souza Teixeira AA	Life Sci	2026	0
Integrative SMR prioritizes oxidative stress-related regulatory genes for Alzhei [PMID:41844011]	Wu L, Dong YT, Mu X, Luo X, Chen ZJ	J Prev Alzheimers Dis	2026	0
Decoding microRNA-Protein Interaction Networks in Alzheimer's Disease: Molecular [PMID:41918207]	Mishra R, Gupta JK	Curr Alzheimer Res	2026	0
Di-2-ethylhexylphthalate-induced miR155-5P promotes placental ferroptosis. [PMID:41937013]	Gu X, Sun F, Li Y, Yang S, Li Y	Int J Biol Macromol	2026	0
Extracellular Vesicles in Obesity: From Pathophysiological Mediators to Therapeu [PMID:41977323]	Pavlović N, Todorović P, Maglica M, Kopi	Int J Mol Sci	2026	0
Insulin resistance and SIRT1 dysregulation in neurodegenerative diseases. [PMID:41759326]	Shah A, Doshi G	Ageing research reviews	2026	0
Urolithin A Reverses Intranigral Rotenone-Generated Parkinsonism by Modulating D [PMID:41880654]	Devi A, Singh SB, Srivastava S, Dandekar	ACS chemical neuroscience	2026	0
Microglial Activation Under Hypoxic Conditions in Early Alzheimer's Disease: Can [PMID:41902653]	Merlo S, Lipari CLR, Patti A, Sortino MA	Phytotherapy research : PTR	2026	0
Subtype-specific sirtuin expression signatures link mitochondrial-epigenetic net [PMID:41692938]	Ungvari Z, Menyhárt O, Ocana A, Lehoczki	GeroScience	2026	0
All the Way: A Decade of SIRT1 in Breast Cancer. [PMID:41898317]	Pratelli G, Montalbano M, Affranchi F, O	Biomedicines	2026	0

Debates (0)

Multi-agent debates referencing this entity

No debates reference this entity

Related Research

Hypotheses and analyses mentioning IR in their description or question text

Closed-loop tACS targeting EC-II PV interneurons to suppress burst firing and bl

Score: 0.857 · Alzheimer's disease · 2026-04-05

## Mechanistic Overview Closed-loop tACS targeting EC-II PV interneurons to suppress burst firing and block tau propagat

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

miR-155/Interferon-gamma Feedback Loop as a Reversible Molecular Switch for Prot

Score: 0.843 · neurodegeneration · 2026-04-16

## Mechanistic Overview miR-155/Interferon-gamma Feedback Loop as a Reversible Molecular Switch for Protective Microglia

Circadian Glymphatic Entrainment via Targeted Orexin Receptor Modulation

Score: 0.841 · neurodegeneration · 2026-04-02

## Mechanistic Overview Circadian Glymphatic Entrainment via Targeted Orexin Receptor Modulation starts from the claim t

Sequential Iron Chelation (Deferoxamine) and GPX4 Restoration (Sulforaphane) Pre

Score: 0.838 · neurodegeneration · 2026-04-17

## Mechanistic Overview Sequential Iron Chelation (Deferoxamine) and GPX4 Restoration (Sulforaphane) Prevents the Self-A

SIRT1 Activation Couples Mitochondrial Biogenesis to Ferroptosis Suppression via

Score: 0.824 · neurodegeneration · 2026-04-17

## Mechanistic Overview SIRT1 Activation Couples Mitochondrial Biogenesis to Ferroptosis Suppression via PGC1alpha-Depen

Hippocampal CA3-CA1 circuit rescue via neurogenesis and synaptic preservation

Score: 0.820 · Alzheimer's disease · 2026-04-02

## Mechanistic Overview Hippocampal CA3-CA1 circuit rescue via neurogenesis and synaptic preservation starts from the cl

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

SIRT1/PGC-1α Axis Activation to Preserve Mitochondrial Resiliency Against Microb

Score: 0.778 · neurodegeneration · 2026-04-16

## Mechanistic Overview SIRT1/PGC-1α Axis Activation to Preserve Mitochondrial Resiliency Against Microbiome-Induced Neu

Prefrontal sensory gating circuit restoration via PV interneuron enhancement

Score: 0.775 · Alzheimer's disease · 2026-04-02

## Molecular Mechanism and Rationale Parvalbumin-expressing (PV+) interneurons represent the most abundant class of GAB

Alpha-gamma cross-frequency coupling enhancement to restore thalamo-cortical mem

Score: 0.775 · Alzheimer's disease · 2026-04-12

## Mechanistic Overview Alpha-gamma cross-frequency coupling enhancement to restore thalamo-cortical memory circuits sta

H3: SIRT1 Insufficiency Disconnects Metabolic Sensing from Epigenomic Homeostasi

Score: 0.770 · neurodegeneration · 2026-04-22

## Mechanistic Overview H3: SIRT1 Insufficiency Disconnects Metabolic Sensing from Epigenomic Homeostasis starts from th

Direct Toxicity Hypothesis: β-Amyloid Directly Impairs Cholinergic Signaling

Score: 0.769 · unknown disease · 2026-04-12

## Mechanistic Overview Direct Toxicity Hypothesis: β-Amyloid Directly Impairs Cholinergic Signaling starts from the cla

Circadian Clock-Autophagy Synchronization

Score: 0.763 · neurodegeneration · 2026-04-02

## Mechanistic Overview Circadian Clock-Autophagy Synchronization starts from the claim that modulating CLOCK within the

APOE4 astrocytes exhibit impaired cholesterol efflux via ABCA1/ABCG1 transporter

Score: 0.760 · neuroscience · 2026-04-22

## Mechanistic Overview APOE4 astrocytes exhibit impaired cholesterol efflux via ABCA1/ABCG1 transporters, driving intra

IR

Understanding Entity Pages

Wiki Pages (20)

Epigenetic-Metabolic Coupling: SIRT1 Activator + NAD+ Precursor

TPIRC - Tau Pathology and Immunotherapy Research Center

BIRC5 (Survivin)

SIRT1 Signaling Pathway in Alzheimer's Disease

IRL757 for Parkinson's Disease Apathy

VIRMA (KIAA1429) in Neurodegeneration

SPAM1-SIRT6 Positive Allosteric Modulator in Neurodegeneration

SPAM1: SIRT6 Positive Allosteric Modulator

SIRT1 Activators for Parkinson's Disease

SIRT7 Gene

SIRT1 Protein

IREB2 — Iron Responsive Element Binding Protein 2

SIRT5 - Sirtuin 5

CD47-SIRPα Immune Checkpoint Therapy

fNIRS Brain-Computer Interface

SIRT3 Protein - Mitochondrial Sirtuin

G Protein-Activated Inward Rectifier Potassium Channel 1 (GIRK1/KCNJ3)

SIRT2 Gene

SIRT2 Modulation Therapy

IRF3 Protein