gene

REST

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about REST: 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.

348Connections

30Hypotheses

8Analyses

50Outgoing

50Incoming

16Experiments

9Debates

Summary

REST is a gene implicated in neurodegeneration research. Key relationships include: regulates, activates, associated with. Associated with ALS, Aging, Als. Connected to 157 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	REST
Full Name	RE1-Silencing Transcription Factor
Chromosome	4q12
Protein Type	Transcription Factor
Function	REST (also known as NRSF) is a zinc-finger transcription factor that represses neuronal gene expression in non-neuronal cells and regulates synaptic plasticity in neurons.
Pathways	Autophagy, Circadian Rhythm, Epigenetic, Immune Response, Lipid Metabolism
UniProt ID	Q9Y2W1
NCBI Gene ID	5978
Ensembl ID	ENSG00000100647
OMIM	600571
GeneCards	REST
Human Protein Atlas	REST
Associated Diseases	AD (cytoplasmic sequestration), Aging, Als, Alzheimer, Alzheimer's disease, Ataxia
Interactions	ALZHEIMER, ALZHEIMER'S DISEASE, AMPK, AND, APOER2, APOPTOSIS
SciDEX Hypotheses	REST Complex Dysregulation as Master Epigenetic Sw REST-like neuronal silencing programs suppress MAP
KG Connections	348 knowledge graph edges
Databases	GeneCards HPA STRING

🔮 Predicted Structure: REST — AlphaFold Q9Y2W1 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (2)

Knowledge base pages for this entity

Canonical Page

REST Gene

gene · 720 words

→

SS18L1 (CREST) (SS18L1)

gene · 826 words

→

Pathway Diagram

graph TD
    REST["REST"] -->|"protects against"| Dementia["Dementia"]
    REST["REST"] -->|"regulates"| OGDHL["OGDHL"]
    REST["REST"] -.->|"inhibits"| Alzheimer["Alzheimer"]
    REST["REST"] -.->|"inhibits"| Ms["Ms"]
    REST["REST"] -.->|"inhibits"| Als["Als"]
    REST["REST"] -.->|"inhibits"| Aging["Aging"]
    CD2AP["CD2AP"] -->|"activates"| REST["REST"]
    NRF2["NRF2"] -->|"activates"| REST["REST"]
    CLOCK["CLOCK"] -->|"regulates"| REST["REST"]
    GENES["GENES"] -->|"regulates"| REST["REST"]
    style REST fill:#4a1a6b,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (252)

Target	Relation	Type	Str
Parkinson	associated_with	disease	0.85
SYP	co_expressed_with	protein	0.75
Alzheimer	associated_with	disease	0.75
Als	regulates	disease	0.75
Aging	associated_with	disease	0.75
Als	associated_with	disease	0.75
Als	inhibits	disease	0.75
Cancer	therapeutic_target	disease	0.75
Tumor	inhibits	disease	0.75
miR-132/212 cluster	inhibits	gene	0.70
oxidative stress response	participates_in	pathway	0.70
neurodegeneration	associated_with	disease	0.70
aging	associated_with	process	0.70
NRF2-mediated antioxidant response	regulates	pathway	0.70
pro-apoptotic gene programs	inhibits	pathway	0.70
Alzheimer's disease transcriptional dysregulation	regulates	disease	0.70
neuronal death	causes	phenotype	0.70
neuronal vulnerability in Alzheimer's disease	regulates	phenotype	0.70
calcium homeostasis	regulates	process	0.70
Neuronal survival in aging	regulates	phenotype	0.70
neuronal survival	protects_against	phenotype	0.70
miR-132/212 repression	activates	process	0.70
neurodegeneration	protective_against	disease	0.70
PARKINSON	associated_with	gene	0.70
PARKINSON'S DISEASE	associated_with	gene	0.70
histone hyperacetylation at neuronal promoters	inhibits	phenotype	0.70
AD (cytoplasmic sequestration)	associated_with	disease	0.70
pro-apoptotic and oxidative stress genes	associated_with	gene	0.70
Lung Cancer	activates	disease	0.65
Aging	inhibits	disease	0.65
Alzheimer	regulates	disease	0.65
Inflammation	activates	disease	0.65
Aging	regulates	disease	0.65
ALS	activates	disease	0.65
Neuroinflammation	expressed_in	disease	0.65
Neuroinflammation	activates	disease	0.65
neurons	expressed_in	cell_type	0.65
Alzheimer	activates	disease	0.65
Dementia	regulates	disease	0.65
Ms	activates	disease	0.65
Parkinson	causes	disease	0.65
Inflammation	expressed_in	disease	0.65
Cancer	activates	disease	0.65
Parkinson	biomarker_for	disease	0.65
ALS	inhibits	disease	0.65
Amyotrophic Lateral Sclerosis	biomarker_for	disease	0.65
Obesity	regulates	disease	0.65
Alzheimer	inhibits	disease	0.65
Ms	inhibits	disease	0.65
Chronic Kidney Disease	associated_with	disease	0.65

Incoming (96)

Source	Relation	Type	Str
GENES	regulates	gene	0.70
PARKINSON'S DISEASE	associated_with	gene	0.70
aging	inhibits	gene	0.70
PARKINSON	associated_with	gene	0.70
CLOCK	regulates	gene	0.60
REELIN	activates	gene	0.60
OPTN	causes	gene	0.60
BDNF	causes	gene	0.60
RIPK3	regulates	gene	0.60
MLKL	regulates	gene	0.60
RIPK1	regulates	gene	0.60
P62	regulates	gene	0.60
BDNF	inhibits	gene	0.60
PSD95	inhibits	gene	0.60
ALZHEIMER'S DISEASE	inhibits	gene	0.60
NEURON	inhibits	gene	0.60
NEURODEGENERATIVE DISORDERS	therapeutic_target	gene	0.60
SYNAPTIC PRUNING	therapeutic_target	gene	0.60
CD2AP	activates	gene	0.60
RNA	activates	gene	0.60
P38	inhibits	gene	0.60
AGING	regulates	gene	0.60
DEMENTIA	regulates	gene	0.60
ALZHEIMER	regulates	gene	0.60
ALZHEIMER'S DISEASE	regulates	gene	0.60
NRSF	activates	gene	0.60
MITOCHONDRIAL DYSFUNCTION	activates	gene	0.60
OXIDATIVE STRESS	activates	gene	0.60
MITOPHAGY	activates	gene	0.60
NEURON	activates	gene	0.60
MITOCHONDRIA	associated_with	gene	0.60
MITOCHONDRIA	inhibits	gene	0.60
CANCER	therapeutic_target	gene	0.60
PARKINSON'S DISEASE	biomarker_for	gene	0.60
PARKINSON	biomarker_for	gene	0.60
NEURODEGENERATIVE DISEASES	biomarker_for	gene	0.60
INFLAMMATION	biomarker_for	gene	0.60
ALS	associated_with	gene	0.60
MOTOR NEURONS	biomarker_for	gene	0.60
EXERCISE	activates	gene	0.60
COMPLEMENT	activates	gene	0.60
SYNAPSE	inhibits	gene	0.60
EGFR	associated_with	gene	0.60
PTEN	inhibits	gene	0.60
TP53	inhibits	gene	0.60
EGFR	activates	gene	0.60
MTOR	activates	gene	0.60
NEURODEGENERATION	activates	gene	0.60
NEURODEGENERATION	associated_with	gene	0.60
ALZHEIMER	associated_with	gene	0.60

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 optogenetic targeting PV interneurons to restore	0.959	alzheimers	Circuit-level neural dynamics in neurode
Closed-loop transcranial focused ultrasound targeting EC-II	0.955	alzheimers	Circuit-level neural dynamics in neurode
Cortico-Striatal Synchrony Restoration via NMDA Modulation	0.950	neuroscience	Circuit-level neural dynamics in neurode
Gamma entrainment therapy to restore hippocampal-cortical sy	0.946	alzheimers	Circuit-level neural dynamics in neurode

Closed-loop transcranial focused ultrasound to restore hippo	0.912	alzheimers	Circuit-level neural dynamics in neurode
APOE-Dependent Autophagy Restoration	0.895	neurodegeneration	Survival Analysis of AD Patient Cohorts:
p38α Inhibitor and PRMT1 Activator Combination to Restore Ph	0.895	neurodegeneration	What is the therapeutic window between i
Optimized Temporal Window for Metabolic Boosting Therapy Det	0.887	neurodegeneration	How do different microglial subtypes (DA
Closed-loop tACS targeting EC-II parvalbumin interneurons to	0.869	alzheimers	Circuit-level neural dynamics in neurode
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
Closed-loop focused ultrasound targeting EC-II PV interneuro	0.863	alzheimers	Circuit-level neural dynamics in neurode
Sequential Iron Chelation (Deferoxamine) and GPX4 Restoratio	0.838	neurodegeneration	Can ferroptosis inhibitors prevent BBB d
Closed-loop transcranial focused ultrasound to restore hippo	0.827	alzheimers	Circuit-level neural dynamics in neurode
Real-time gamma-guided transcranial focused ultrasound targe	0.827	alzheimers	Circuit-level neural dynamics in neurode
TREM2-Dependent Switch Hypothesis: TREM2 Agonism Redirects S	0.813	synaptic-biology	Does SPP1-mediated synaptic engulfment r
SLC7A11 System Activation Restores Cystine Uptake and GSH Sy	0.812	neurodegeneration	Can ferroptosis inhibitors prevent BBB d
Targeting the Mechanistic Link Between AQP4 Dysfunction and	0.803	neurodegeneration	Can ferroptosis inhibitors prevent BBB d
Closed-loop transcranial focused ultrasound targeting CA1 PV	0.797	alzheimers	Circuit-level neural dynamics in neurode
NMN Supplementation Restores SIRT1/p66Shc/FOXO3 Epigenetic A	0.790	neurodegeneration	epigenetic reprogramming aging neurons
Gamma entrainment reactivates PV+ interneuron ensembles to r	0.777	alzheimers	Gamma entrainment therapy to restore hip
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
Thalamocortical Synchrony Restoration via NMDA Modulation	0.774	neuroscience	Circuit-level neural dynamics in neurode
Chromatin Accessibility Restoration via BRD4 Modulation	0.768	neurodegeneration	Epigenetic reprogramming in aging neuron
Closed-loop transcranial focused ultrasound to restore hippo	0.767	alzheimers	Circuit-level neural dynamics in neurode
Chromatin Remodeling-Mediated Nutrient Sensing Restoration	0.764	neurodegeneration	Epigenetic reprogramming in aging neuron
Closed-loop transcranial focused ultrasound to restore hippo	0.000	alzheimers	Circuit-level neural dynamics in neurode
Closed-loop transcranial focused ultrasound with gamma entra	0.000	alzheimers	Circuit-level neural dynamics in neurode

Mentioning Analyses (8)

Scientific analyses that reference this entity

Which specific transcription factors mediate MAPT suppression during proteostati

neurodegeneration | 2026-04-25 | 3 hypotheses Top: 0.624

Comparative epigenetic signatures: DNA methylation age acceleration and histone

neurodegeneration | 2026-04-18 | 7 hypotheses Top: 0.620

Gene Regulatory Network Inference in Alzheimer's Disease

neurodegeneration | 2026-04-16 | 1 hypotheses Top: 0.661

Comparative epigenetic signatures across AD, PD, and ALS

neurodegeneration | 2026-04-16 | 7 hypotheses Top: 0.550

Do tau strains or regional cellular environments primarily drive PSP vs CBD path

neurodegeneration | 2026-04-10 | 0 hypotheses

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
Tet2 modulation in Aβ42-injured mouse hippocampal neurons	exploratory	Alzheimer's disease	0.900	0.00	primary mouse hippocampal neur	proposed	N/A
iPSC-NPC effects on astrocytes in vitro ICH model	exploratory	intracerebral hemorrhage	0.900	0.00	in vitro ICH cell culture mode	completed	N/A
MAPK pathway inhibition by QTJD through butyrate mechanism	exploratory	Mycoplasma pneumoniae pneumoni	0.900	0.00	Mouse macrophages	proposed	N/A
AMPK knockdown validation experiment	exploratory	intracerebral hemorrhage	0.880	0.00	astrocyte cell culture	proposed	N/A
P2RY12-MTOR pathway interaction in VSMCs	exploratory	atherosclerosis	0.850	0.00	cultured VSMCs	proposed	N/A
iPSC-NPC transplantation in ICH animal model	validation	intracerebral hemorrhage	0.850	0.00	animal ICH model	proposed	N/A
Brain Connectivity-Targeted tACS Trial in Early AD	clinical	Alzheimer's Disease	0.509	0.50	human postmortem brain tissue	proposed	$520,000
s:** - Test whether HCN1 knockout specifically in EC layer II accelera	falsification	Alzheimer's Disease	0.400	0.50	cell_line	proposed	$80,000
AD Amyloid-Resilient Phenotype Study — Why Some amyloid-Positive Indiv	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$6,550,000
AD Combination Therapy Trial: Anti-Aβ + Anti-Tau	clinical	Alzheimer's Disease	0.400	0.50	cell_line	proposed	$180,000
Biomarker-Guided Sequential Therapy Selection in Alzheimer's Disease	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
tACS Connectivity Trial in Early Alzheimer's	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
Brain Connectivity-Targeted tACS Trial in Early AD	clinical	Alzheimer's Disease	0.400	0.50	mouse	proposed	$730,000
Cognitive Reserve Mechanisms in Alzheimer's Disease — Molecular Basis	clinical	Alzheimer's Disease	0.400	0.50	human	completed	$6,550,000
Cholinergic System Dysfunction in DLB — Mechanisms and Therapeutic Res	clinical	Alzheimer's Disease	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
Complement C1q/C3-CR3 signaling pathway mediates abnormal microglial phagocytosi [PMID:38642614]	Han QQ, Shen SY, Liang LF, Chen XR, Yu J	Brain Behav Immun	2024	1
Metabolic orchestration of cell death by AMPK-mediated phosphorylation of RIPK1. [PMID:37384704]	Zhang T, Xu D, Trefts E, Lv M, Inuzuka H	Science	2023	1
Replating Induces mTOR-Dependent Rescue of Protein Synthesis in Charcot-Marie-To [PMID:41876253]	Koenig J, McGuire A, Homedan Y, Alberhas	eNeuro	2026	0
S-equol promotes ferroptosis in triple negative breast cancer by coordinating NC [PMID:41925800]	Ni F, Huang Z, Cui Y, Huang P, Xue Z, Hu	Molecular and cellular biochem	2026	0
Anatomical and neurochemical profiles of somatostatin-positive neurons in the mo [PMID:41796787]	Tomioka R, Kobayashi K, Song WJ	Neuroscience	2026	0
Subtype-Specific Roles of Anterior Cingulate Cortex Neurons in Pain-Induced Soci [PMID:41799202]	Wan X, Yan Z, Zhang Z, Liu X, Yang D, Zh	Theranostics	2026	0
Metabolic dysregulation reshapes the immune landscape: The gut microbiota-mTOR a [PMID:41445190]	Li J, Li J, Chen K	Mol Ther	2026	0
Senecavirus a VP2 protein orchestrates PRDX1 degradation through dual autophagy [PMID:41479169]	Li Z, Yang X, Mao J, Zeng P, Qi Y et al.	Autophagy	2026	0
Inhibition of mTOR Enhances the Efficacy of Proteasome-Dependent Targeted Protei [PMID:41529091]	Liu Y, Sun Y, Song TY, Ni SY, Pu YS et a	Cancer Res	2026	0
Microglial metabolic reprogramming in Alzheimer's disease: Pathways, mechanisms, [PMID:41651180]	Yang FG, Yang H, Han SW, Wang JT, Gao W	Ageing Res Rev	2026	0
mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential [PMID:41789635]	Huo R, Yang Y, Wei C, Yang Y, Meng D et	Int J Mol Med	2026	0
Microcystin-LR-induced phosphorylation imbalance and organelle stress: An integr [PMID:41846138]	Teng Z, Shahzad A, Xu Z, Xia J, Zhang J	J Hazard Mater	2026	0
Copper deficiency impairs oligodendrocyte maturation and social behavior via mit [PMID:41920999]	Usui N, Doi M, Berto S, Matsuoka K, Ishi	Sci Adv	2026	0
A comparative analysis of pig-to-rhesus corneal xenotransplantation with various [PMID:41928466]	Lee SH, Yoon CH, Choi HJ, Lee HJ, Kang H	Korean J Ophthalmol	2026	0
Crosstalk between inflammation and autophagy in CeD organoids. [PMID:41933042]	Bellomo C, Furone F, Auricchio R, D'Anie	Sci Rep	2026	0
Epigenetically regulated pancreatic GABA-somatostatin signaling underlies gestat [PMID:41779871]	Zhu H, Luo S, Liu C, Cheng Y, Ren Z, Mo	Science translational medicine	2026	0
Therapeutic Potential of Somatostatin and Its Analogues in Alzheimer's Disease: [PMID:41854733]	Liu K, Zhang XY, Wang YT, Wang R, Jin RH	Molecular neurobiology	2026	0
Targeting the AKT/mTOR axis: pectolinarigenin induces autophagy and apoptosis in [PMID:41924135]	Fang Y, Bai J, Bo S, Cui X, Song H, Guo	Frontiers in pharmacology	2026	0
Targeting the GSK-3β/mTOR axis: a novel pharmacological strategy for preeclampsi [PMID:41922823]	Alshaikh ABA, Al-Kuraishy HM, Abdelaziz	Naunyn-Schmiedeberg's archives	2026	0
Platelet proteomic signatures of amyloid β-positive mild cognitive impairment an [PMID:41904574]	Cho YE, Kim A, Lee HM, Oh JW, Son SJ, Ro	Molecular brain	2026	0

Debates (9)

Multi-agent debates referencing this entity

Which specific transcription factors mediate MAPT suppression during proteostati

closed · Rounds: 4 · Score: 0.66 · 2026-04-25

Investigate mechanisms of epigenetic reprogramming in aging neurons

closed · Rounds: 4 · Score: 0.79 · 2026-04-22

The core debate question remains unresolved - whether intrinsic tau conformation

closed · Rounds: 4 · Score: 0.30 · 2026-04-21

Which transcription factors drive the gene regulatory networks that distinguish

closed · Rounds: 4 · Score: 0.70 · 2026-04-21

Investigate shared DNA methylation age acceleration and histone modification pat

closed · Rounds: 4 · Score: 1.00 · 2026-04-20

What are the shared DNA methylation age acceleration and histone modification pa

closed · Rounds: 4 · Score: 0.50 · 2026-04-18

Is REST the master regulator of neuronal vulnerability in AD, or is it one of se

closed · Rounds: 4 · Score: 0.70 · 2026-04-16

Astrocyte reactivity subtypes in neurodegeneration

closed · Rounds: 4 · Score: 0.95 · 2026-04-10

Evaluate the potential of CRISPR/Cas9 and related gene editing technologies for

closed · Rounds: 4 · Score: 0.95 · 2026-04-03

Related Research

Hypotheses and analyses mentioning REST in their description or question text

REST

Understanding Entity Pages

Summary

Wiki Pages (2)

REST Gene

SS18L1 (CREST) (SS18L1)

Pathway Diagram

Outgoing (252)

Incoming (96)

Targeting Hypotheses (30)

Mentioning Analyses (8)

Which specific transcription factors mediate MAPT suppression during proteostati

Comparative epigenetic signatures: DNA methylation age acceleration and histone

Gene Regulatory Network Inference in Alzheimer's Disease

Comparative epigenetic signatures across AD, PD, and ALS

Do tau strains or regional cellular environments primarily drive PSP vs CBD path

Investigate mechanisms of epigenetic reprogramming in aging neurons

CRISPR-based therapeutic approaches for neurodegenerative diseases

Astrocyte reactivity subtypes in neurodegeneration

Experiments (16)

Related Papers (20)

Debates (9)

Which specific transcription factors mediate MAPT suppression during proteostati

Investigate mechanisms of epigenetic reprogramming in aging neurons

The core debate question remains unresolved - whether intrinsic tau conformation

Which transcription factors drive the gene regulatory networks that distinguish

Investigate shared DNA methylation age acceleration and histone modification pat

What are the shared DNA methylation age acceleration and histone modification pa

Is REST the master regulator of neuronal vulnerability in AD, or is it one of se

Astrocyte reactivity subtypes in neurodegeneration

Evaluate the potential of CRISPR/Cas9 and related gene editing technologies for

Related Research

Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscilla

APOE-Dependent Autophagy Restoration

p38α Inhibitor and PRMT1 Activator Combination to Restore Physiological TDP-43 P

Optimized Temporal Window for Metabolic Boosting Therapy Determines Success of M

Closed-loop tACS targeting EC-II parvalbumin interneurons to restore gamma rhyth

Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscilla

Optogenetic restoration of hippocampal gamma oscillations via selective PV inter

Closed-loop focused ultrasound targeting EC-II PV interneurons to restore theta-

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

Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscilla

Real-time gamma-guided transcranial focused ultrasound targeting EC-II SST inter

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

SLC7A11 System Activation Restores Cystine Uptake and GSH Synthesis to Prevent N

Targeting the Mechanistic Link Between AQP4 Dysfunction and Ferroptosis Prevents

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