enzyme

HDAC

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about HDAC: 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.

685Connections

18Hypotheses

13Analyses

50Outgoing

50Incoming

9Experiments

14Debates

Summary

HDAC is an entity related to neurodegeneration research. Key relationships include: inhibits, activates, co discussed. Associated with ALS, ALZHEIMER'S DISEASE, Aging. Connected to 104 entities in the SciDEX knowledge graph.

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🔬 Protein Info

Gene Symbol	HDAC
Pathways	Amyloid, Blood-Brain Barrier, Epigenetic, Pi3K/Akt, Wnt
GeneCards	HDAC
Human Protein Atlas	HDAC
Alzheimer's Disease (AD)	~6.5 million Americans, $321 billion annual cost[@alzheimers2024]
Parkinson's Disease (PD)	~1 million Americans, $52 billion annual cost[@parkinsons2024]
Huntington's Disease (HD)	~41,000 Americans[@huntingtons2024]
ALS	~30,000 Americans[@als2024]
HDAC6 inhibitors	Promote clearance of α-synuclein and tau via autophagy[@simes2022]
Class I HDACs	Reduce neuroinflammation and improve synaptic plasticity[@liu2020]
Sirtuin activators	Enhance mitochondrial function and stress resistance[@singh2023]
Associated Diseases	aging, Als, Alzheimer, Alzheimer's disease, Amyotrophic Lateral Sclerosis
Known Drugs/Compounds	aducanumab, donanemab, HDAC inhibitors, lecanemab, rapamycin, valproic acid
Interactions	ACLY, Actin, Adiponectin, AGING, AKT, ALS
SciDEX Hypotheses	Astrocyte-Mediated Neuronal Epigenetic Rescue
KG Connections	685 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

Wiki Pages (21)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    HDAC["HDAC"] -.->|"inhibits"| Gene_Expression["Gene Expression"]
    HDAC["HDAC"] -->|"modulates"| Chromatin_Structure["Chromatin Structure"]
    HDAC["HDAC"] -->|"involved in"| Nervous_System["Nervous System"]
    HDAC["HDAC"] -->|"regulates"| Histone_Lysine_Acetylation["Histone Lysine Acetylation"]
    HDAC["HDAC"] -->|"involved in"| Pathological_Processes["Pathological Processes"]
    HDAC["HDAC"] -->|"contributes to"| Cognitive_Decline["Cognitive Decline"]
    HDAC_Inhibitors["HDAC Inhibitors"] -.->|"inhibits"| HDAC["HDAC"]
    Butyrate["Butyrate"] -.->|"inhibits"| HDAC["HDAC"]
    h_8fe389e8["h-8fe389e8"] -->|"targets"| HDAC["HDAC"]
    AND["AND"] -->|"activates"| HDAC["HDAC"]
    style HDAC fill:#006494,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (444)

Target	Relation	Type	Str
HDAC inhibitors	therapeutic_target	drug	0.95
gene transcription	regulates	process	0.95
chromatin architecture	modulates	process	0.95
epigenetic regulation	participates_in	pathway	0.80
aging	inhibits	disease	0.70
oxidative stress response	participates_in	pathway	0.70
cortex	expressed_in	brain_region	0.70
neural stem cells	inhibits	cell_type	0.70
Alzheimer's disease	treats	disease	0.70
Alzheimer's disease	inhibits	disease	0.70
Neuroinflammation	inhibits	disease	0.65
Parkinson	inhibits	disease	0.65
Alzheimer	regulates	disease	0.65
Inflammation	implicated_in	disease	0.65
Als	activates	disease	0.65
ALS	inhibits	disease	0.65
ALS	associated_with	disease	0.65
Parkinson	regulates	disease	0.65
Alzheimer	therapeutic_target	disease	0.65
Autoimmune	inhibits	disease	0.65
Cancer	inhibits	disease	0.65
Huntington	regulates	disease	0.65
synaptic plasticity	participates_in	pathway	0.65
Neuroinflammation	implicated_in	disease	0.65
Alzheimer	inhibits	disease	0.65
Aging	inhibits	disease	0.65
Inflammation	inhibits	disease	0.65
insulin signaling	participates_in	pathway	0.65
Neurodegeneration	contributes_to	disease	0.65
Ms	therapeutic_target	disease	0.65
neurodegeneration	inhibits	disease	0.65
Fibrosis	activates	disease	0.65
Ms	activates	disease	0.65
Anxiety	activates	disease	0.65
Depression	activates	disease	0.65
Spinal Cord Injury	activates	disease	0.65
Ms	expressed_in	disease	0.65
Parkinson	activates	disease	0.65
Neurodegeneration	inhibits	disease	0.65
Ms	associated_with	disease	0.65
Amyotrophic Lateral Sclerosis	associated_with	disease	0.65
Als	associated_with	disease	0.65
Neurodegeneration	causes	disease	0.65
neurotrophin signaling	participates_in	pathway	0.65
HDAC1	inhibits	gene	0.65
IL-10	activates	gene	0.65
TGF	activates	gene	0.65
unfolded protein response	participates_in	pathway	0.65
TGF-beta signaling	participates_in	pathway	0.65
Tumor	associated_with	disease	0.65

Incoming (241)

Source	Relation	Type	Str
h-8fe389e8	targets	hypothesis	0.90
ALZHEIMER'S DISEASE	inhibits	gene	0.74
ALZHEIMER'S DISEASE	associated_with	disease	0.74
TNF	associated_with	gene	0.66
IL-6	associated_with	gene	0.66
GDNF	activates	gene	0.65
JUN	inhibits	gene	0.60
HDAC4	associated_with	gene	0.60
HDAC2	activates	gene	0.60
EXERCISE	activates	gene	0.60
CAMKII	activates	gene	0.60
ALZHEIMER	activates	gene	0.60
HDAC3	expressed_in	gene	0.60
HDAC3	regulates	gene	0.60
DNA	regulates	gene	0.60
LOX	activates	gene	0.60
GENES	activates	gene	0.60
DNA	activates	gene	0.60
ALZHEIMER'S DISEASE	activates	gene	0.60
TNF-Α	activates	gene	0.60
CYTOKINES	activates	gene	0.60
NEUROINFLAMMATION	implicated_in	gene	0.60
ALZHEIMER	causes	gene	0.60
TAU	regulates	gene	0.60
DNA	implicated_in	gene	0.60
SIRT5	regulates	gene	0.60
SIRT7	associated_with	gene	0.60
IL-1	activates	gene	0.60
MAP2	activates	gene	0.60
TNF	activates	gene	0.60
E2F7	inhibits	gene	0.60
HDAC2	expressed_in	gene	0.60
AR	inhibits	gene	0.60
HUNTINGTON	regulates	gene	0.60
MTOR	therapeutic_target	gene	0.60
NOTCH	therapeutic_target	gene	0.60
HIPPO	therapeutic_target	gene	0.60
HEDGEHOG	therapeutic_target	gene	0.60
AKT	activates	gene	0.60
ALS	activates	gene	0.60
ATM	expressed_in	gene	0.60
BDNF	expressed_in	gene	0.60
CDK5	expressed_in	gene	0.60
GSK3	expressed_in	gene	0.60
TP53	inhibits	gene	0.60
YAP	inhibits	gene	0.60
PARKINSON'S DISEASE	inhibits	gene	0.60
RB1	inhibits	gene	0.60
HDAC6	inhibits	gene	0.60
HDAC1	inhibits	gene	0.60

Targeting Hypotheses (18)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Selective HDAC3 Inhibition with Cognitive Enhancement	0.779	neurodegeneration	Epigenetic reprogramming in aging neuron
Astrocyte-Mediated Neuronal Epigenetic Rescue	0.725	neurodegeneration	Epigenetic reprogramming in aging neuron
Gut-BBB Axis: Tributyrin/Butyrate HDAC Inhibition Epigenetic	0.712	-	Blood-brain barrier permeability changes
HDAC3-Selective Inhibition for Clock Reset	0.710	neurodegeneration	Epigenetic clocks and biological aging i
HDAC6 Activation as SCFA-Mediated Neuroprotective Mechanism	0.682	neurodegeneration	Do SCFAs directly modulate α-synuclein a

HDAC2 Phospho-Lock Window for Synaptic Gene Silencing	0.643	neurodegeneration	What is the optimal therapeutic window d
HDAC6 Selective Inhibition to Restore Acetylation Balance an	0.643	structural biology	What is the atomic-resolution structure
CX3CR1-Targeted HDAC3 Knockdown in Microglia via AAV9 Delive	0.620	pharmacology	How can CNS-selective HDAC/DNMT inhibito
HDAC3-Dependent A1 Astrocyte Commitment Window	0.611	neurodegeneration	What is the optimal therapeutic window d
Brain-Ester Prodrug Strategy for CNS-Selective HDAC6 Inhibit	0.570	pharmacology	How can CNS-selective HDAC/DNMT inhibito
Direct neuronal HDAC inhibition is unlikely to mediate thera	0.560	neurodegeneration	Do physiological concentrations of SCFAs
HDAC1/2 Complex Restoration Corrects Age-Related Histone Hyp	0.520	neurodegeneration	Investigate mechanisms of epigenetic rep
HDAC6 Inhibition for Dual Restoration of Microtubule Stabili	0.484	neurodegeneration	Which tau PTMs are both disease-specific
Microglial Priming Window for HDAC1-Dependent DAM Transition	0.463	neurodegeneration	What is the optimal therapeutic window d
HDAC6 Inhibitor Therapy for Pan-Neurodegenerative Protein Ho	0.450	neurodegeneration	Comparative epigenetic signatures across
MITF Acts as the Primary Transcriptional Effector Downstream	0.444	neurodegeneration	How does HDAC1/2 deletion specifically e
LncRNA-HDAC1 Complex Formation Locks Microglia in Primed Sta	0.420	developmental neurobiology	Do perinatal immune challenges create pe
HDAC2-Specific Repression of PU.1 Pioneer Factor Target Site	0.415	neurodegeneration	How does HDAC1/2 deletion specifically e

Mentioning Analyses (13)

Scientific analyses that reference this entity

What molecular mechanisms mediate HDAC9's effects on Aβ deposition and synaptic

neurodegeneration | 2026-04-15 | 1 hypotheses Top: 0.740

What molecular mechanisms mediate HDAC9's effects on Aβ deposition and synaptic

neurodegeneration | 2026-04-14 | 0 hypotheses

How does HDAC1/2 deletion specifically enhance microglial amyloid phagocytosis c

neurodegeneration | 2026-04-13 | 2 hypotheses Top: 0.444

What is the atomic-resolution structure of K280-acetylated tau and how does it t

structural biology | 2026-04-13 | 1 hypotheses Top: 0.643

What is the optimal therapeutic window during preclinical AD for epigenetic repr

neurodegeneration | 2026-04-07 | 7 hypotheses Top: 0.643

Experiments (9)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Epigenetic clocks association with brain aging patterns in older women	exploratory	cognitive impairment and demen	0.900	0.00	human patients	proposed	N/A
Proposed experiment from debate on Epigenetic clocks and biological ag	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$100,000
Mechanism: Why Does Amyloid Removal Only Slow Decline 27%?	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$7,500,000
Animal Model Comparison for Neurodegenerative Disease Therapeutics	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$7,100,000
Epigenetic Dysregulation in Huntington's Disease — Therapeutic Targeti	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
Epigenetic Regulation Dysfunction in Alzheimer's and Parkinson's Disea	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$7,500,000
Proposed experiment from debate on Microglia activate astrocytes via I	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$100,000
CRISPR Gene Correction Approaches for CBS/PSP	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Effect of Electronic Prescribing Compared to Paper-Based (Handwritten) Prescribi [PMID:34433219]	Aluga D, Nnyanzi LA, King N, Okolie EA,	Appl Clin Inform	2021	1
Structurally diverse sesquiterpenoids from the aerial parts of Artemisia annua ( [PMID:32891001]	Qin DP, Li HB, Pang QQ, Huang YX, Pan DB	Bioorg Chem	2020	1
Mycobacterium Abscessus: A Rare Cause of Peri-Ductal Mastitis in Endemic Regions [PMID:32580856]	Shaikh A, Vohra LM	J Coll Physicians Surg Pak	2020	1
The scanning ion conductance microscope for cellular physiology. [PMID:23086993]	Lab MJ, Bhargava A, Wright PT, Gorelik J	Am J Physiol Heart Circ Physio	2013	1
Telomere dysfunction causes sustained inflammation in chronic obstructive pulmon [PMID:21885626]	Amsellem V, Gary-Bobo G, Marcos E, Maitr	Am J Respir Crit Care Med	2011	1
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's diseas [PMID:21102463]	Franke A, McGovern DP, Barrett JC, Wang	Nat Genet	2010	1
HDAC3 Preserves the primordial follicle reserve by epigenetically suppressing fe [PMID:41803516]	["Chen Z", "Guo J", "Gao M", "Wang H", "	Cellular and molecular life sc	2026	0
Determination of the effects of [PMID:41823023]	["Yir\u00fcn A", "\u00c7ak\u0131r D", "E	Journal of Alzheimer's disease	2026	0
Discovery of a Covalent HDAC3 Degrader with Excellent Anti-Inflammatory Activity [PMID:41812251]	["Qin H", "Shi Y", "Liu R", "Wang B", "G	Journal of medicinal chemistry	2026	0
Myeloid HDAC3 deletion protects against traumatic optic injury. [PMID:41851071]	Shahror RA, Morris CA, Cunningham A, Chu	Cell death discovery	2026	0
HDAC3 mediates retinal endothelial cell metabolic reprogramming and angiogenesis [PMID:41023273]	Mitchell CD, Morris CA, Wild M, Cunningh	Acta Pharmacol Sin	2026	0
Metabolomics identifies riboflavin as a therapeutic agent for acute pancreatitis [PMID:41352543]	Shi Y, Peng J	J Nutr Biochem	2026	0
β-Hydroxybutyrate improves glymphatic system function and alleviates cerebral ed [PMID:41535708]	Yu MJ, Xiong RQ, Wu JW, Li YC, Xie JX et	Acta Pharmacol Sin	2026	0
Epigenetic mechanisms and therapeutic innovations in chronic pain-associated neu [PMID:41554641]	Zhang K, Zhu S, Xing N, Zhou Z, Chen J e	Br J Pharmacol	2026	0
SATB2 Mediates H3K9 Delactylation by Recruiting HDAC3 to Repress LCN2 and Inhibi [PMID:41736683]	Wen T, Yang L, Cai S, Liu Y, Fan J et al	Adv Sci (Weinh)	2026	0
Histone deacetylases: Function in tumor development and therapeutic prospects (R [PMID:41783166]	Lin R, Zhang Y, Li H, Liang F	Oncol Lett	2026	0
Fibroblast histone deacetylase-1 promotes kidney interstitial fibrosis following [PMID:41830491]	Nguyen H, Mendoza LD, Oliver AS, Aldaz K	Am J Physiol Renal Physiol	2026	0
TGF-β mediates epigenetic control of innate antiviral responses and SIV reservoi [PMID:41862649]	Ghneim K, Ten-Caten F, Santana AC, Latif	Nat Immunol	2026	0
LncRNA SNHG5 promotes macrophage lipid accumulation and aggravates atheroscleros [PMID:41844502]	Liu X, Wang HH, Lan XY, Sun SY, Xu XD, H	Biochimica et biophysica acta.	2026	0
HOX code-based stratification reveals RUNX1T1-HDAC reprogramming as a targetable [PMID:41912135]	Jiang Y, Cheng S, Zhang CY, Jin X, Li L,	Cancer letters	2026	0

Debates (14)

Multi-agent debates referencing this entity

The debate identified temporal specificity as a critical weakness - when exactly

closed · Rounds: 4 · Score: 0.68 · 2026-04-21

The abstract shows HDAC9 overexpression reduces Aβ deposition and improves synap

closed · Rounds: 4 · Score: 0.95 · 2026-04-16

The abstract shows HDAC9 overexpression reduces Aβ deposition and improves synap

closed · Rounds: 4 · Score: 0.71 · 2026-04-16

The debate proposed K280 acetylation creates a β-sheet nucleation interface but

closed · Rounds: 4 · Score: 0.86 · 2026-04-14

The debate proposed K280 acetylation creates a β-sheet nucleation interface but

closed · Rounds: 4 · Score: 0.74 · 2026-04-14

While the study shows HDAC1/2 deletion improves amyloid clearance and cognition,

closed · Rounds: 4 · Score: 0.95 · 2026-04-13

Epigenetic reprogramming in aging neurons

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

Sleep disruption as cause and consequence of neurodegeneration

closed · Rounds: 4 · Score: 0.91 · 2026-04-06

Epigenetic clocks and biological aging in neurodegeneration

closed · Rounds: 4 · Score: 0.93 · 2026-04-06

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 HDAC in their description or question text

HDAC

Understanding Entity Pages

Summary

Wiki Pages (21)

HDAC Inhibitors for Neurodegeneration — Investment Landscape

HDAC6 Protein

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HDAC Inhibitor Mechanism in Neurodegeneration

HDAC6 Modulation Therapy for Neurodegeneration

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HDAC7 Protein (Histone Deacetylase 7)

HDAC5 (Histone Deacetylase 5) Protein

HDAC11 Gene

HDAC2 Protein — Histone Deacetylase 2

HDAC6 Gene - Histone Deacetylase 6

HDAC5 Gene

Histone Deacetylase (HDAC) Enzymes

Alzheimer's Disease HDAC and Epigenetic Inhibitor Companies

Pathway Diagram

Outgoing (444)

Incoming (241)

Targeting Hypotheses (18)

Mentioning Analyses (13)

What molecular mechanisms mediate HDAC9's effects on Aβ deposition and synaptic

What molecular mechanisms mediate HDAC9's effects on Aβ deposition and synaptic

How does HDAC1/2 deletion specifically enhance microglial amyloid phagocytosis c

What is the atomic-resolution structure of K280-acetylated tau and how does it t

What is the optimal therapeutic window during preclinical AD for epigenetic repr

Epigenetic reprogramming in aging neurons

CRISPR-based therapeutic approaches for neurodegenerative diseases

Circuit-level neural dynamics in neurodegeneration

Cell type vulnerability in Alzheimer's Disease (SEA-AD data - v2)

SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas

Epigenetic clocks and biological aging in neurodegeneration

Sleep disruption as cause and consequence of neurodegeneration

What are the mechanisms by which gut microbiome dysbiosis influences Parkinson's

Experiments (9)

Related Papers (20)

Debates (14)

The debate identified temporal specificity as a critical weakness - when exactly

The abstract shows HDAC9 overexpression reduces Aβ deposition and improves synap

The abstract shows HDAC9 overexpression reduces Aβ deposition and improves synap

The debate proposed K280 acetylation creates a β-sheet nucleation interface but

The debate proposed K280 acetylation creates a β-sheet nucleation interface but

While the study shows HDAC1/2 deletion improves amyloid clearance and cognition,

Epigenetic reprogramming in aging neurons

Sleep disruption as cause and consequence of neurodegeneration

Epigenetic clocks and biological aging in neurodegeneration

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

Related Research

HDAC2 Phospho-Lock Window for Synaptic Gene Silencing

HDAC6 Selective Inhibition to Restore Acetylation Balance and Microtubule Stabil

CX3CR1-Targeted HDAC3 Knockdown in Microglia via AAV9 Delivery

HDAC3-Dependent A1 Astrocyte Commitment Window

Brain-Ester Prodrug Strategy for CNS-Selective HDAC6 Inhibition

Direct neuronal HDAC inhibition is unlikely to mediate therapeutic alpha-synucle

HDAC1/2 Complex Restoration Corrects Age-Related Histone Hypoacetylation

HDAC6 Inhibition for Dual Restoration of Microtubule Stability and Autophagic Ta

Microglial Priming Window for HDAC1-Dependent DAM Transition

HDAC6 Inhibitor Therapy for Pan-Neurodegenerative Protein Homeostasis

MITF Acts as the Primary Transcriptional Effector Downstream of HDAC1/2 Deletion

LncRNA-HDAC1 Complex Formation Locks Microglia in Primed State

HDAC2-Specific Repression of PU.1 Pioneer Factor Target Sites Suppresses the IL-