concept

GPR109A

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about GPR109A: 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.

246Connections

1Hypotheses

4Analyses

50Outgoing

50Incoming

5Experiments

5Debates

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💡 Concept Info

Name	GPR109A
Key Genes/Proteins	AADC, Adiponectin, AGER, AGING, AMPK, App
Related Diseases	aging, Aging, Als, ALS, Alzheimer's disease
Linked Hypotheses	1 hypotheses

Wiki Pages (1)

Knowledge base pages for this entity

GPR109A (HCAR2) Agonists for Neurodegeneration

therapeutic · 557 words

→

Pathway Diagram

graph TD
    GPR109A["GPR109A"]
    style GPR109A fill:#1a237e,stroke:#4fc3f7,stroke-width:3px
    GPR109A -->|"binds"| Beta_Hydroxybutyrate["Beta-Hydroxybutyrate"]
    GPR109A -->|"activates"| PPARG["PPARG"]
    GPR109A -->|"activates"| Depression["Depression"]
    GPR109A -->|"activates"| Parkinson["Parkinson"]
    GPR109A -->|"activates"| Neuroinflammation["Neuroinflammation"]
    GPR109A -->|"activates"| Cancer["Cancer"]
    GPR109A -.->|"protects against"| Als["Als"]
    GPR109A -->|"interacts"| Atherosclerosis["Atherosclerosis"]
    GPR109A -->|"activates"| Neurodegeneration["Neurodegeneration"]
    Esketamine{"Esketamine"} -->|"activates"| GPR109A
    Beta_hydroxybutyrate{"Beta-hydroxybutyrate"} -->|"activates"| GPR109A
    Niacin{"Niacin"} -->|"activates"| GPR109A
    Heme{"Heme"} -->|"binds to"| GPR109A
    Acifran{"Acifran"} -->|"activates"| GPR109A
    DEPRESSION([DEPRESSION]) -->|"activates"| GPR109A
    PARKINSON([PARKINSON]) -->|"activates"| GPR109A
    IL_1([IL-1]) -->|"expressed in"| GPR109A
    NAD([NAD]) -->|"activates"| GPR109A
    TLR4([TLR4]) -->|"activates"| GPR109A

Outgoing (180)

Target	Relation	Type	Str
microglial_activation	regulates	phenotype	0.90
DEPRESSION	mediates	disease	0.80
oxidative stress response	participates_in	pathway	0.80
neurodegeneration	associated_with	disease	0.79
microglia	expressed_in	cell_type	0.70
microglial activation	modulates	process	0.70
microglial phenotype	regulates	mechanism	0.70
Tumor	activates	disease	0.65
ALS	causes	disease	0.65
ALS	protects_against	disease	0.65
Cardiovascular	activates	disease	0.65
Migraine	activates	disease	0.65
ALS	activates	disease	0.65
Tumor	expressed_in	disease	0.65
ALS	associated_with	disease	0.65
Parkinson	regulates	disease	0.65
Inflammation	activates	disease	0.65
Inflammation	regulates	disease	0.65
Inflammation	associated_with	disease	0.65
Carcinoma	activates	disease	0.65
Schizophrenia	expressed_in	disease	0.65
Parkinson	activates	disease	0.65
Diabetes	regulates	disease	0.65
Atherosclerosis	inhibits	disease	0.65
Pyroptosis	inhibits	disease	0.65
Diabetes	activates	disease	0.65
Neurodegeneration	activates	disease	0.65
Aging	activates	disease	0.65
Cancer	regulates	disease	0.65
Neurodegeneration	regulates	disease	0.65
Als	associated_with	disease	0.65
Neurodegeneration	therapeutic_target	disease	0.65
Als	therapeutic_target	disease	0.65
Depression	activates	disease	0.65
Neuroinflammation	activates	disease	0.65
Atherosclerosis	interacts_with	disease	0.65
Als	protects_against	disease	0.65
Als	activates	disease	0.65
Cancer	activates	disease	0.65
neuroinflammation	activates	disease	0.60
Rb	interacts_with	protein	0.60
Cholesterol	activates	pathway	0.60
SIRT2	inhibits	gene	0.60
UCP2	inhibits	gene	0.60
GPR120	associated_with	gene	0.60
Neuroinflammation	modulates	pathway	0.60
Depression	therapeutic_target	disease	0.60
NLRP3	inhibits	gene	0.60
Rb	expressed_in	protein	0.60
NMDA receptor	associated_with	receptor	0.60

Incoming (66)

Source	Relation	Type	Str
h-48775971	targets	hypothesis	0.90
h-3d545f4e	targets	hypothesis	0.90
butyrate	activates	drug	0.70
Butyrate	activates	biomarker	0.70
ketamine	treats	compound	0.70
PPAR	activates	gene	0.60
MET	therapeutic_target	gene	0.60
GSDMD	inhibits	gene	0.60
ketamine	inhibits	compound	0.60
CD14	activates	gene	0.60
TLR2	activates	gene	0.60
TLR4	activates	gene	0.60
ketamine	implicated_in	compound	0.60
ketamine	biomarker_for	compound	0.60
ketamine	expressed_in	compound	0.60
CMKLR1	associated_with	gene	0.60
CXCL12	associated_with	gene	0.60
LDL	activates	gene	0.60
HMGCS2	regulates	gene	0.60
HO-1	activates	gene	0.60
ketamine	activates	compound	0.60
Niacin	activates	drug	0.60
Heme	binds_to	drug	0.60
Acifran	activates	drug	0.60
CXCL11	associated_with	gene	0.60
Beta-hydroxybutyrate	activates	drug	0.60
INFLAMMATION	associated_with	gene	0.60
NEURODEGENERATION	regulates	gene	0.60
EXERCISE	regulates	gene	0.60
GASDERMIN	inhibits	gene	0.60
MICROGLIA	associated_with	gene	0.60
STROKE	protects_against	gene	0.60
Esketamine	activates	drug	0.60
MERTK	activates	gene	0.60
DEPRESSION	activates	gene	0.60
PARKINSON	activates	gene	0.60
IL-1	expressed_in	gene	0.60
NAD	activates	gene	0.60
MICROGLIA	therapeutic_target	gene	0.60
GASDERMIN	therapeutic_target	gene	0.60
PYROPTOSIS	inhibits	gene	0.60
IL-1	activates	gene	0.60
PER	inhibits	gene	0.60
GSH	activates	gene	0.60
NEUROINFLAMMATION	activates	gene	0.60
IL-10	activates	gene	0.60
RNA	activates	gene	0.60
AGING	activates	gene	0.60
NEURODEGENERATION	activates	gene	0.60
EXERCISE	activates	gene	0.60

Targeting Hypotheses (1)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Targeted Butyrate Supplementation for Microglial Phenotype M	0.805	neurodegeneration	What are the mechanisms by which gut mic

Mentioning Analyses (4)

Scientific analyses that reference this entity

Does reduced Prevotellaceae abundance cause PD pathology or result from it?

neurodegeneration | 2026-04-11 | 7 hypotheses

What brain concentrations of SCFAs are achieved via oral probiotics and are they

pharmacokinetics | 2026-04-11 | 0 hypotheses

Neuroinflammation and microglial priming in early Alzheimer's Disease

neurodegeneration | 2026-04-04 | 20 hypotheses Top: 0.651

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

neurodegeneration | 2026-04-01 | 13 hypotheses Top: 0.924

Experiments (5)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
GPR109A receptor validation using knockout macrophages	exploratory	Mycoplasma pneumoniae pneumoni	0.920	GPR109A knockout mouse macroph	proposed	N/A
Periodontitis-induced colonic inflammation in mice	validation	Periodontitis and intestinal i	0.900	C57BL/6J mice	proposed	N/A
Fecal microbiota transplantation from periodontitis donors	validation	Periodontitis-associated gut d	0.900	Germ-free mice with fecal micr	proposed	N/A
GPR109A functional modulation with pharmacological agents	validation	Periodontitis with intestinal	0.880	C57BL/6J mice with ligature-in	proposed	N/A
Probiotic CBM588 supplementation rescue experiment	validation	Periodontitis-associated intes	0.850	C57BL/6J mice with periodontit	proposed	N/A

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
GPR109a-AMPK axis mediates the Attenuation of uric acid-induced M1 macrophage po [PMID:41882026]	Du M, He Y, Zhu Y, Chen W, Chen X, Yang	Scientific reports	2026
Gut microbiota-derived isovaleric acid alleviates atrial fibrillation by suppres [PMID:41638192]	Ding N, Wu H, Hua Y, Hua R, Li B, Xie Y,	Cell metabolism	2026
Therapeutic strategies for hypertension: exploring the role of microbiota-derive [PMID:40637840]	Tortelote GG	Pediatr Nephrol	2026
Xin-Jia-Tong-Xie-Yao-Fang restores the intestinal barrier to alleviate irritable [PMID:41655800]	Zhu J, Yang L, Fang Z, Chen J, Fu R, Liu	Microbial pathogenesis	2026
Cranberry extract-supplemented microbiota effluents enhance intestinal barrier i [PMID:41680408]	Cattero V, Mayer T, Veilleux A, Roussel	Scientific reports	2026
Qingfei Tongluo Jiedu Formula Regulates M2 Macrophage Polarization via the Butyr [PMID:41754753]	Liu Z, Fan Q, Sun R, Jiang Y	Pharmaceuticals (Basel, Switze	2026
Periodontitis promotes intestinal inflammation through gut microbiota-mediated s [PMID:41816355]	Wang X, Xu Z, Yao Y, Jia H, Du M, Wang S	Frontiers in cellular and infe	2026
Hydroxycarboxylic acid receptor 2 (GPR109A) and retinopathies: pathways and pros [PMID:41889514]	Lester J, Amamoo R, Thounaojam MC, Marti	Frontiers in medicine	2026
Exercise-induced β-hydroxybutyrate contributes to cognitive improvement in aging [PMID:41421649]	Wang L, Mao L, Zhu D, Li K, Gao H, Zhou	Journal of sport and health sc	2025
Chaperone-mediated autophagy, heat shock protein 70, and serotonin: novel target [PMID:40319428]	["Mohamed R", "Abdallah D", "El-Abhar H"	Inflammopharmacology	2025
Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bo [PMID:40305364]	Suresh VV, Sivaprakasam S, Bhutia YD, Pr	Biomolecules	2025
β-Hydroxybutyrate Regulates Activated Microglia to Alleviate Neurodegenerative P [PMID:36771231]	Jayashankar SS, Tajul Arifin K, Nasarudd	Nutrients	2023
Bacterial factors required for Streptococcus pneumoniae coinfection with influen [PMID:34452635]	Chen YY, Huang CT, Li SW, Pan YJ, Lin TL	Journal of biomedical science	2021
Face masks considerably reduce COVID-19 cases in Germany. [PMID:33273115]	Mitze T, Kosfeld R, Rode J, Wälde K	Proceedings of the National Ac	2020
Serum neuronal exosomes predict and differentiate Parkinson's disease from atypi [PMID:32273329]	Jiang C, Hopfner F, Katsikoudi A, Hein R	Journal of neurology, neurosur	2020
Adapting Drosophila melanogaster Cell Lines to Serum-Free Culture Conditions. [PMID:33028628]	Luhur A, Mariyappa D, Klueg KM, Buddika	G3 (Bethesda, Md.)	2020
Massive Hemoptysis and Recurrent Infective Endocarditis in Intravenous Drug user [PMID:33154920]	Almutairi MD, El-Ghoneimy YA, Alghamdi A	Journal of the Saudi Heart Ass	2020
Surgical approach to a left-sided gallbladder. [PMID:31420438]	Pereira R, Perera M, Roberts M, Avramovi	BMJ case reports	2019
Comparison of tension band wiring and other tibial tuberosity advancement techni [PMID:31578143]	McCartney W, Ober C, Benito M, MacDonald	Acta veterinaria Scandinavica	2019
Predictive Role of High Blood Pressure for the Incidence of Metabolic Syndrome. [PMID:31261156]	Presta V, Miceli F, Tocci G	Cardiology	2019

Debates (5)

Multi-agent debates referencing this entity

The debate highlighted that while SCFAs can cross the blood-brain barrier, the a

closed · Rounds: 4 · Score: 0.50 · 2026-04-20

Investigate mechanistic links between early microglial priming states, neuroinfl

closed · Rounds: 4 · Score: 0.86 · 2026-04-12

Investigate mechanistic links between early microglial priming states, neuroinfl

closed · Rounds: 5 · Score: 0.95 · 2026-04-12

Does reduced Prevotellaceae abundance cause PD pathology or result from it?

closed · Rounds: 4 · Score: 0.95 · 2026-04-11

What are the mechanisms underlying what are the mechanisms by which gut microbio

closed · Rounds: 4 · Score: 0.95 · 2026-04-01

Related Research

Hypotheses and analyses mentioning GPR109A in their description or question text

No additional research found