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

14Experiments

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	30 hypotheses

Wiki Pages (20)

Knowledge base pages for this entity

Validated Hypothesis: SIRT1 Activation Couples Mitochondrial Biogenesis to Ferroptosis Suppression via PGC1alpha-Dependent GPX4 Upregulation in Post-CA Brain

hypothesis · 4606 words

→

Validated Hypothesis: SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senescence

hypothesis · 4455 words

→

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
senescence	participates_in	pathway	0.60
TGF	interacts_with	gene	0.60
TGF-beta signaling	participates_in	pathway	0.60
neurodegeneration	associated_with	disease	0.60
MAP2	interacts_with	gene	0.60
NLRP3	activates	gene	0.60
LRP2	targets	gene	0.60
LRP2	regulates	gene	0.60
diabetes	activates	disease	0.60
PI3K-AKT-mTOR signaling	participates_in	pathway	0.60
LDL	associated_with	gene	0.60
synaptic plasticity	participates_in	pathway	0.60
pyroptosis	participates_in	pathway	0.60
apoptosis pathway	participates_in	pathway	0.60
ubiquitin-proteasome	participates_in	pathway	0.60
diabetes	protects_against	disease	0.60
PINK	activates	gene	0.60
TNF	activates	gene	0.60
stroke	activates	disease	0.60
blood-brain barrier	participates_in	pathway	0.60
neurodegeneration	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
TH	expressed_in	gene	0.60
JNK	activates	gene	0.60
NBS1	inhibits	gene	0.60
PARP1	inhibits	gene	0.60
RAD51	inhibits	gene	0.60
Alzheimer's disease	associated_with	disease	0.60
diabetes	associated_with	disease	0.60
oxidative stress response	participates_in	pathway	0.60
Alzheimer's disease	activates	disease	0.60
MAPK signaling	participates_in	pathway	0.60
PI3K	activates	gene	0.60
RNA	interacts_with	gene	0.60
neurons	expressed_in	cell_type	0.55
microglia	expressed_in	cell_type	0.55
astrocytes	expressed_in	cell_type	0.55

Incoming (26)

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

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Microglial-Mediated Tau Clearance Dysfunction via TREM2 Rece	0.937	neuroscience	Circuit-level neural dynamics in neurode
SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senesc	0.893	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
Circadian Glymphatic Entrainment via Targeted Orexin Recepto	0.882	neurodegeneration	Perivascular spaces and glymphatic clear
Closed-loop transcranial focused ultrasound to restore hippo	0.865	alzheimers	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
Sequential Iron Chelation (Deferoxamine) and GPX4 Restoratio	0.838	neurodegeneration	Can ferroptosis inhibitors prevent BBB d
Gamma entrainment repairs cross-regional phase-amplitude cou	0.826	alzheimers	Gamma entrainment therapy to restore hip
miR-33 Antisense Oligonucleotide Hyper-Lipidation Strategy	0.824	molecular-biology	Is APOE4's reduced lipid binding pathoge
SIRT1 Activation Couples Mitochondrial Biogenesis to Ferropt	0.824	neurodegeneration	Can ferroptosis inhibitors prevent BBB d
Hippocampal CA3-CA1 circuit rescue via neurogenesis and syna	0.820	alzheimers	Circuit-level neural dynamics in neurode
Kinetic Modeling Predicts Threshold-Dependent Efficacy—Early	0.815	protein-folding	Can chaperone enhancement approaches ove
TREM2-Dependent Switch Hypothesis: TREM2 Agonism Redirects S	0.813	synaptic-biology	Does SPP1-mediated synaptic engulfment r
Closed-loop tACS targeting EC-II PV interneurons to suppress	0.811	alzheimers	Circuit-level neural dynamics in neurode
MATR3 Nuclear Body Disruption Impairs RNA Processing Hubs an	0.801	als	-
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	Gut Microbiome Analysis in Parkinson's D
Prefrontal sensory gating circuit restoration via PV interne	0.775	alzheimers	Circuit-level neural dynamics in neurode
Alpha-gamma cross-frequency coupling enhancement to restore	0.775	alzheimers	Circuit-level neural dynamics in neurode
Dual-Circuit Tau Vulnerability Cascade	0.774	neuroscience	Circuit-level neural dynamics in neurode
H3: SIRT1 Insufficiency Disconnects Metabolic Sensing from E	0.770	neurodegeneration	Investigate mechanisms of epigenetic rep
METTL3-Mediated m6A Modification of lncRNA-0021 Regulates mi	0.769	molecular-neurobiology	How does lncRNA-0021 achieve sequence-sp
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
Cholinergic Basal Forebrain-Hippocampal Circuit Protection	0.760	neuroscience	Circuit-level neural dynamics in neurode
APOE4 astrocytes exhibit impaired cholesterol efflux via ABC	0.758	neuroscience	APOE4-driven lipid metabolism dysregulat
Dopaminergic Ventral Tegmental-Hippocampal Circuit Protectio	0.751	neuroscience	Circuit-level neural dynamics in neurode
Iron-driven lipid peroxidation and GPX4 failure create a fer	0.750	neurodegeneration	What mechanisms drive the self-amplifyin
GBA1-Deficiency Disrupts Mitochondrial- Lysosomal Contact Si	0.747	neurodegeneration	-
Circulating Soluble PDGFRβ Reflects Pericyte Loss and Preced	0.745	-	What blood-brain barrier permeability ch

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (14)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
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
Irisin effects on osteogenic differentiation in mesenchymal stem cells	exploratory	bone fracture	0.900	0.00	mouse bone mesenchymal stem ce	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
Anti-miR-155 LNA Oligonucleotide Shifts Microglia to Homeostatic State	in_vivo	neurodegeneration	0.774	0.65	C57BL/6J LPS model (chronic i.	proposed	$58,000
Sequential DFO + Sulforaphane Prevents Iron-Ferroptosis Cascade in Rat	in_vivo	post-cardiac-arrest neurodegen	0.768	0.72	Sprague-Dawley rat asphyxial c	abandoned	$48,000
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
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
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
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
Decoding microRNA-Protein Interaction Networks in Alzheimer's Disease: Molecular [PMID:41918207]	Mishra R, Gupta JK	Current Alzheimer research	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
Signal transduction, dimerization, and therapeutic targeting of Orexin and recep [PMID:41383480]	Zhang S, Wang P, Ji B, Shao Y, Hou S et	Front Pharmacol	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
Increased Neuronal Expression of the Early Endosomal Adaptor APPL1 Replicates Al [PMID:40514243]	Jiang Y, Sachdeva K, Goulbourne CN, Berg	The Journal of neuroscience :	2025	0
Bioinformatic analysis of neuropeptide related genes in patients diagnosed with [PMID:39437604]	Yay F, Ayan D	Comput Biol Med	2024	0
Effects of Paradoxical Sleep Deprivation on MCH and Hypocretin Systems. [PMID:39698172]	Agamme ALDA, Tufik S, Torterolo P, D'Alm	Sleep science (Sao Paulo, Braz	2024	0
Blast Exposure Induces Acute Alterations in Circadian Clock Genes in the Hypotha [PMID:41127649]	Govindarajulu M, Patel MY, Krishnan J, L	Neurotrauma reports	2023	0
Contextual generalization of social stress learning is modulated by orexin recep [PMID:35724928]	Yaeger JDW, Krupp KT, Summers TR, Summer	Neuropharmacology	2022	0
Evaluation of the α-casein (CSN1S1) locus as a potential target for a site-speci [PMID:35568783]	["Smirnov A", "Kontsevaya G", "Shnaider	Scientific reports	2022	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

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

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

Gamma entrainment repairs cross-regional phase-amplitude coupling via CA1 Schaff

Score: 0.826 · alzheimers · 2026-04-28

Auditory 40 Hz entrainment applied during NREM sleep consolidates temporal coupling between hippocampal theta oscillatio

miR-33 Antisense Oligonucleotide Hyper-Lipidation Strategy

Score: 0.824 · molecular-biology · 2026-04-16

## Mechanistic Overview miR-33 Antisense Oligonucleotide Hyper-Lipidation Strategy starts from the claim that modulating

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 · alzheimers · 2026-04-02

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

Kinetic Modeling Predicts Threshold-Dependent Efficacy—Early Intervention Requir

Score: 0.815 · protein-folding · 2026-04-22

**Molecular Mechanism and Rationale** The therapeutic hypothesis centers on the kinetic constraints governing chaperone

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

Score: 0.813 · synaptic-biology · 2026-04-21

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

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

Score: 0.811 · alzheimers · 2026-04-05

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

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 · alzheimers · 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 · alzheimers · 2026-04-12

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

Dual-Circuit Tau Vulnerability Cascade

Score: 0.774 · neuroscience · 2026-04-07

## Mechanistic Overview Dual-Circuit Tau Vulnerability Cascade starts from the claim that modulating MAPT within the dis

IR

Understanding Entity Pages

Wiki Pages (20)

Validated Hypothesis: SIRT1 Activation Couples Mitochondrial Biogenesis to Ferroptosis Suppression via PGC1alpha-Dependent GPX4 Upregulation in Post-CA Brain

Validated Hypothesis: SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senescence

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