protein

DAT

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about DAT: 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.

69Connections

30Hypotheses

0Analyses

49Outgoing

20Incoming

19Experiments

0Debates

Summary

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🔬 Protein Info

Gene Symbol	DAT
Protein Family	Na+/Cl- dependent neurotransmitter transporter (SLC6)
Function	Dat Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Molecular Weight	~79 kDa (glycosylated)
Pathways	dopamine neurotransmission, membrane diffusion, vesicular traffic
UniProt ID	Q01959
GeneCards	DAT
Human Protein Atlas	DAT
Associated Diseases	ALS, Alzheimer's disease, Levodopa-Induced Motor Complications, Parkinson, Parkinson's disease
Known Drugs/Compounds	curcumin, levodopa
Interactions	AND, ANKK1, COMT, DRD2, EN1, EN2
KG Connections	69 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🔮 Predicted Structure: DAT — AlphaFold Q01959 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (5)

Knowledge base pages for this entity

Pathway Diagram

graph TD
    DAT["DAT"]
    Als{"Als"}
    DAT -->|"biomarker_for"| Als
    Parkinson{"Parkinson"}
    DAT -->|"biomarker_for"| Parkinson
    ALS{"ALS"}
    DAT -->|"biomarker_for"| ALS
    SUMF1(["SUMF1"])
    DAT -->|"biomarker_for"| SUMF1
    GBA(["GBA"])
    DAT -->|"activates"| GBA
    AADC(["AADC"])
    DAT -->|"biomarker_for"| AADC
    DDC(["DDC"])
    DDC -->|"biomarker_for"| DAT
    GBA_MUTATIONS(["GBA MUTATIONS"])
    GBA_MUTATIONS -->|"activates"| DAT
    PARKINSON(["PARKINSON"])
    PARKINSON -->|"biomarker_for"| DAT
    LRRK2(["LRRK2"])
    LRRK2 -->|"activates"| DAT
    style DAT fill:#1a3a4a,stroke:#4fc3f7,stroke-width:3px,color:#4fc3f7

Outgoing (49)

Target	Relation	Type	Str
dopamine neurotransmission	regulates	process	0.95
striatal axonal compartments	expressed_in	cell_type	0.90
medial forebrain bundle	expressed_in	structure	0.90
membrane diffusion	involved_in	process	0.85
vesicular traffic	involved_in	process	0.75
Parkinson	biomarker_for	disease	0.65
Als	biomarker_for	disease	0.65
ALS	biomarker_for	disease	0.65
Rb	biomarker_for	protein	0.60
App	biomarker_for	protein	0.60
DDC	biomarker_for	gene	0.60
SUMF1	biomarker_for	gene	0.60
GBA	activates	gene	0.60
AADC	biomarker_for	gene	0.60
PARKINSON	biomarker_for	gene	0.60
AND	activates	gene	0.60
PARKINSON'S DISEASE	biomarker_for	gene	0.60
DRD2	associated_with	gene	0.60
ALS	associated_with	disease	0.60
Parkinson	associated_with	disease	0.60
DDC	regulates	gene	0.60
TH	associated_with	gene	0.60
PARKIN	expressed_in	gene	0.60
TH	expressed_in	gene	0.60
oxidative stress response	participates_in	pathway	0.60
ubiquitin-proteasome	participates_in	pathway	0.60
DRD2	interacts_with	gene	0.60
Parkinson's disease	regulates	disease	0.60
VMAT2	interacts_with	gene	0.60
Parkinson's disease	interacts_with	disease	0.60
VMAT2	associated_with	gene	0.60
Levodopa-Induced Motor Complications	associated_with	phenotype	0.60
Alzheimer's disease	associated_with	disease	0.60
PITX3	activates	gene	0.55
LMX1A	activates	gene	0.55
NURR1	activates	gene	0.55
TH	activates	gene	0.55
Parkinson's disease	associated_with	disease	0.55
NURR1	regulates	gene	0.55
TH	regulates	gene	0.55
VMAT2	regulates	gene	0.55
dopaminergic neurons	expressed_in	cell_type	0.55
neurons	expressed_in	cell_type	0.55
EN1	activates	gene	0.55
EN2	activates	gene	0.55
FOXA2	activates	gene	0.55
IPSC	protects_against	cell_type	0.35
GBA1	activates	gene	0.35
LRRK2	activates	gene	0.35

Incoming (20)

Source	Relation	Type	Str
VPS35	interacts_with	protein	0.85
RETROMER COMPLEX	mediates	protein	0.80
lysosomes	degrades	organelle	0.80
BHBA	upregulates	compound	0.70
GBA MUTATIONS	activates	gene	0.60
PARKINSON	biomarker_for	gene	0.60
LRRK2	activates	gene	0.60
DDC	biomarker_for	gene	0.60
COMT	associated_with	gene	0.60
ANKK1	interacts_with	gene	0.60
COMT	interacts_with	gene	0.60
AADC	biomarker_for	gene	0.60
SUMF1	biomarker_for	gene	0.60
GBA	activates	gene	0.60
ANKK1	associated_with	gene	0.60
curcumin	targets	drug	0.60
ABCA1	biomarker_for	gene	0.60
levodopa	targets	drug	0.55
AADC	regulates	gene	0.55
DDC	associated_with	gene	0.35

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Selective APOE4 Degradation via Proteolysis Targeting Chimer	0.795	neurodegeneration	APOE4 structural biology and therapeutic
ALOX15-Driven Enzymatic Ferroptosis in AD Oligodendrocytes v	0.777	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
Iron-driven lipid peroxidation and GPX4 failure create a fer	0.750	neurodegeneration	What mechanisms drive the self-amplifyin
miR-33 Antisense Oligonucleotide Hyper-Lipidation Strategy	0.741	molecular biology	Is APOE4's reduced lipid binding pathoge
SGMS1-Driven Sphingomyelin Accumulation Impairs BACE1 Lysoso	0.734	neurodegeneration	What molecular mechanisms link elevated

Senescence-Induced Lipid Peroxidation Spreading	0.730	neurodegeneration	Senolytic therapy for age-related neurod
Selective LXRβ agonists restore ABCA1/ABCG1 expression and A	0.710	neuroscience	APOE4-driven lipid metabolism dysregulat
Autophagy-Lysosomal Degradation of IBA1 in Stressed Microgli	0.706	neuroinflammation	What causes IBA1 low/negative microglia
FOXO3-Pioneer Factor Complex Stabilizes Heterochromatin Unde	0.700	neurodegeneration	Investigate mechanisms of epigenetic rep
TREM2-APOE Axis Manipulation via APOE Lipidation for DAM Rec	0.685	neurodegeneration	Microglial subtypes in neurodegeneration
APOE4 hypolipidation and ABCA1 mistrafficking impair cholest	0.680	molecular biology	Does APOE4's reduced lipid-binding direc
LXRβ-Selective Agonism to Simultaneously Enhance APOE Lipida	0.655	lipidomics	Lipid metabolism dysregulation in Alzhei
HBOT at 1.5 ATA for 60 min induces hormetic response via Nrf	0.640	neurodegeneration	What are the optimal oxygen pressure, du
Amyloid-beta induces secondary pericyte senescence after con	0.640	neurodegeneration	Does pericyte senescence drive BBB break
APOE4-Targeted Ultrasonic Lipidation Enhancement for Gamma O	0.625	Alzheimer's disease	-
Chaperone-Degradation Coupling Prevents Aggregate Persistenc	0.620	protein folding	Can chaperone enhancement approaches ove
Upstream restoration of glial lipid efflux and apoE lipidati	0.590	molecular biology	Does APOE4's reduced lipid-binding direc
CSF p-tau217 Normalization Reflects Amyloid-Driven Tau Patho	0.586	neurodegeneration	-
Liproxstatin-1 as Mechanism-Validation Tool for Ferroptosis	0.580	neurodegeneration	Can ferroptosis inhibitors prevent BBB d
CHIP-mediated ubiquitination selectively targets oligomeric	0.580	protein biochemistry	Do chaperones selectively recognize path
APOE4 drives astrocyte metabolic reprogramming toward glycol	0.580	neuroscience	APOE4-driven lipid metabolism dysregulat
APOE4 Isoform Correction via Lipidation Enhancement as CTE R	0.552	neurodegeneration	What genetic risk factors predispose ind
Real-time closed-loop transcranial focused ultrasound target	0.542	Alzheimer's disease	Circuit-level neural dynamics in neurode
PLIN2 (Perilipin-2) Degradation via Autophagy Activation to	0.535	lipidomics	Lipid metabolism dysregulation in Alzhei
Lamin B1 Degradation as Irreversibility Gate	0.523	molecular biology	What is the optimal therapeutic window t
NRF2 Activation to Counteract Oxidative Stress from RGS6 Def	0.518	neurodegeneration	Does RGS6 upregulation or D2 autorecepto
C1q-Mediated Delivery of miR-33 Antisense Oligonucleotides f	0.489	molecular biology	Is APOE4's reduced lipid binding pathoge
SREBP-2 Direct Inhibition Hyper-Lipidation Strategy	0.489	molecular biology	Is APOE4's reduced lipid binding pathoge
USP14 Inhibition to Accelerate Proteasomal Degradation of Sy	0.481	proteomics	Quantitative proteomics of the aging syn
CHIP E3 Ligase Enhancement to Target Synaptic Proteins for D	0.472	proteomics	Quantitative proteomics of the aging syn

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
GWAS of plasma NfL in East Asian cohort	exploratory	Alzheimer's disease	0.950	0.00	human patients - East Asian co	proposed	N/A
GWAS of plasma pTau217 in East Asian cohort	exploratory	Alzheimer's disease	0.950	0.00	human patients - East Asian co	proposed	N/A
Dairy intake and dementia risk in Malmö Diet and Cancer cohort	clinical	Alzheimer's disease	0.950	0.00	Swedish community-based adults	proposed	N/A
GWAS of plasma pTau181 in East Asian cohort	exploratory	Alzheimer's disease	0.950	0.00	human patients - East Asian co	proposed	N/A
GWAS of plasma GFAP in East Asian cohort	exploratory	Alzheimer's disease	0.950	0.00	human patients - East Asian co	proposed	N/A
KEEPS Continuation: Long-term effects of menopausal hormone therapy on	clinical	Alzheimer's disease	0.950	0.00	recently menopausal women with	proposed	N/A
GWAS of composite biomarker score	exploratory	Alzheimer's disease	0.900	0.00	human patients - East Asian co	proposed	N/A
RBG treatment in ApoE-/- atherosclerosis mouse model	validation	atherosclerosis	0.900	0.00	ApoE-/- mice	proposed	N/A
Bioinformatics analysis and hub gene identification	exploratory	Alzheimer's disease	0.800	0.00	computational analysis of tran	proposed	N/A
s:** - Biochemical binding assays measuring PROTAC selectivity for APO	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$100,000
Why Does Amyloid Removal Only Slow Decline 27%? — Mechanistic investig	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$7,100,000
Proposed experiment from debate on Senolytics targeting p16/p21+ senes	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000
Biomechanical Impact Profiles and Chronic Traumatic Encephalopathy Phe	clinical	Neurodegeneration	0.400	0.50	in_silico	proposed	$180,000
Ferroptosis Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Iron Dyshomeostasis in MSA Pathogenesis Experiment	validation	Neurodegeneration	0.400	0.50	human	proposed	$2,280,000
Peroxisomal Dysfunction Validation in Parkinson's Disease	validation	Parkinson's Disease	0.400	0.50	human	proposed	$2,280,000
Peroxisome Dysfunction Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Regulated Necrosis Validation Study in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Traumatic Brain Injury and Alzheimer's Disease Relationship	validation	Alzheimer's Disease	0.400	0.50	human	proposed	$3,000,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Klebsiella pneumoniae Induces Ferroptosis and Lactation Dysfunction in Bovine Ma [PMID:40937759]	Mao P, Wang Z, Duan J, Dong P, Yuan C, L	J Agric Food Chem	2025	1
Targeting ferroptosis: novel therapeutic approaches and intervention strategies [PMID:41425591]	Luo Y, Long M, Wu X, Zeng L	Front Immunol	2025	1
Trimetazidine attenuates Ischemia/Reperfusion-Induced myocardial ferroptosis by [PMID:39134283]	Tan M, Yin Y, Chen W, Zhang J, Jin Y, Zh	Biochem Pharmacol	2024	1
Amelioration of Tau and ApoE4-linked glial lipid accumulation and neurodegenerat [PMID:37995685]	Litvinchuk A, Suh JH, Guo JL, Lin K, Dav	Neuron	2024	1
The cell biology of APOE in the brain. [PMID:37805344]	Windham IA, Cohen S	Trends Cell Biol	2024	1
The APOE-R136S mutation protects against APOE4-driven Tau pathology, neurodegene [PMID:37957317]	Maxine R Nelson, Peng Liu, Ayushi Agrawa	Nature neuroscience	2023	1
APOE and Alzheimer's disease: advances in genetics, pathophysiology, and therape [PMID:33340485]	Serrano-Pozo A, Das S, Hyman BT	Lancet Neurol	2021	1
Lysosome-targeting chimaeras for degradation of extracellular proteins. [PMID:32728216]	Banik SM, Pedram K, Wisnovsky S, Ahn G,	Nature	2020	1
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies. [PMID:31564456]	Long JM, Holtzman DM	Cell	2019	1
Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. [PMID:31367008]	Yamazaki Y, Zhao N, Caulfield TR, Liu CC	Nat Rev Neurol	2019	1
Plasma GFAP outperforms CSF GFAP in detecting amyloid pathology and is associate [PMID:41905188]	Cetindag AC, Schipke CG, Esselmann H, Kr	The journal of prevention of A	2026	0
Discovery of a glycosylated colchicine derivative as a neuroprotective agent for [PMID:41455281]	["Jash M", "Gupta S", "Garg S", "Khan J"	European journal of medicinal	2026	0
The NADPH oxidase inhibitor Vas2870 prevents myocyte ferroptosis and improves ca [PMID:41671579]	Wang J, Li CM, Yang B, Tantai RN, Guo HX	British journal of pharmacolog	2026	0
Perioperative polygenic and APOE-based genetic risk assessment for neurocognitiv [PMID:40562635]	Thedim M, Hu J, Maher M, Wiener-Kronish	Br J Anaesth	2026	0
Increased genetic protection against Alzheimer's disease in centenarians. [PMID:40615639]	Bae H, Song Z, Ali A, Sasaki T, Tesi N e	Geroscience	2026	0
Integrative machine learning approach to risk prediction for dementia and Alzhei [PMID:40864401]	Stern A, Linial M	Geroscience	2026	0
Adipose Tissue Macrophage-Derived Proplatelet Basic Protein Exacerbates Psoriasi [PMID:40886963]	Zhu L, Du L, Wu J, Ding D, Wang J et al.	J Invest Dermatol	2026	0
Restoration of p53 mRNA combined with BRD4 silencing by brain targeted nanocapsu [PMID:41101204]	Sang Y, Cao Y, Li S, Quan Y, Wang S et a	Biomaterials	2026	0
Targeting KAT8 alleviates vascular senescence by modulating the INHBA/TGF-β path [PMID:41445196]	Lin Z, Xiong J, Zhang F, Zhang H, Zhu M	Mol Ther	2026	0
Menopause, cognition, and Alzheimer's disease risk. [PMID:41531227]	Samudra N, Vemuri M, Weitlauf J	Curr Opin Obstet Gynecol	2026	0

Debates (0)

Multi-agent debates referencing this entity

No debates reference this entity

Related Research

Hypotheses and analyses mentioning DAT in their description or question text

Senescence-Induced Lipid Peroxidation Spreading

Score: 0.730 · neurodegeneration · 2026-04-02

## Mechanistic Overview Senescence-Induced Lipid Peroxidation Spreading starts from the claim that modulating GPX4/SLC7A

Selective LXRβ agonists restore ABCA1/ABCG1 expression and APOE lipidation in AP

Score: 0.710 · neuroscience · 2026-04-22

**Molecular Mechanism and Rationale** The molecular basis for selective liver X receptor beta (LXRβ/NR1H2) agonism in A

Autophagy-Lysosomal Degradation of IBA1 in Stressed Microglia

Score: 0.706 · neuroinflammation · 2026-04-21

## Mechanistic Overview Autophagy-Lysosomal Degradation of IBA1 in Stressed Microglia starts from the claim that modulat

FOXO3-Pioneer Factor Complex Stabilizes Heterochromatin Under Oxidative Stress

Score: 0.700 · neurodegeneration · 2026-04-21

## **Molecular Mechanism and Rationale** The FOXO3-SIRT1 regulatory axis represents a sophisticated cellular defense me

TREM2-APOE Axis Manipulation via APOE Lipidation for DAM Recruitment

Score: 0.685 · neurodegeneration · 2026-04-25

Strongest mechanistic support among all hypotheses. TREM2-TYROBP signaling for DAM transition well-established. AL002 Ph

APOE4 hypolipidation and ABCA1 mistrafficking impair cholesterol efflux and seco

Score: 0.680 · molecular biology · 2026-04-24

A plausible upstream submechanism is that lipid-poor APOE4 disrupts ABCA1 trafficking, likely via ARF6-associated endoso

LXRβ-Selective Agonism to Simultaneously Enhance APOE Lipidation and Reduce Micr

Score: 0.655 · lipidomics · 2026-04-25

LXRβ-Selective Agonism to Simultaneously Enhance APOE Lipidation and Reduce Microglial Cholesterol Accumulation

HBOT at 1.5 ATA for 60 min induces hormetic response via Nrf2 activation, enhanc

Score: 0.640 · neurodegeneration · 2026-04-25

This hypothesis posits that mild hyperbaric oxidative stress activates Nrf2-ARE transcriptional programs, upregulating S

Amyloid-beta induces secondary pericyte senescence after contractile and oxidati

Score: 0.640 · neurodegeneration · 2026-04-25

Soluble Aβ oligomers trigger endothelin-1 and ROS-dependent pericyte contractile stress, and repeated exposure converts

Chaperone-Degradation Coupling Prevents Aggregate Persistence by Shunting Seeds

Score: 0.620 · protein folding · 2026-04-22

**Molecular Mechanism and Rationale** The chaperone-degradation coupling hypothesis centers on the critical interaction

Upstream restoration of glial lipid efflux and apoE lipidation will outperform d

Score: 0.590 · molecular biology · 2026-04-24

As a translational thesis, the debate supports prioritizing upstream correction of glial lipid handling over blunt direc

Liproxstatin-1 as Mechanism-Validation Tool for Ferroptosis Inhibition

Score: 0.580 · neurodegeneration · 2026-04-25

Liproxstatin-1 (Lip-1) inhibits ferroptosis upstream of GPX4 by blocking lipoxygenase-mediated lipid peroxidation, prese

CHIP-mediated ubiquitination selectively targets oligomeric pathologic conformer

Score: 0.580 · protein biochemistry · 2026-04-21

**Molecular Mechanism and Rationale** The carboxy terminus of Hsc70-interacting protein (CHIP, encoded by STUB1) functi

DAT