Entity Detail — Knowledge Graph Node
This page aggregates everything SciDEX knows about BDNF: 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.
Brain-Derived Neurotrophic Factor (BDNF) is the most abundant neurotrophin in the brain, essential for neuronal survival, synaptic plasticity, and memory formation. BDNF signals through TrkB receptor to activate PI3K/Akt, MAPK/ERK, and PLCgamma pathways, promoting long-term potentiation (LTP) and dendritic growth. BDNF levels decline in Alzheimer's, Parkinson's, Huntington's, and major depression. The Val66Met polymorphism (rs6265) impairs activity-dependent BDNF secretion and is associated with reduced hippocampal volume and episodic memory deficits. Exercise robustly increases BDNF levels, providing a mechanistic link between physical activity and cognitive resilience. Therapeutic strategies include BDNF mimetics, TrkB agonists, and lifestyle interventions to boost endogenous BDNF.
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| Gene Symbol | BDNF |
| Full Name | Brain-Derived Neurotrophic Factor |
| Chromosome | 11p14.1 |
| Protein Family | Neurotrophin family |
| Protein Type | Ligand |
| Target Class | Ligand |
| Function | Protein replacement therapy or small molecule mimetic |
| Mechanism of Action | Protein replacement therapy or small molecule mimetic |
| Primary Expression | Secreted, Synaptic vesicles |
| Druggability | Low (0.29) |
| Clinical Stage | Phase II |
| Pathways | Akt, Apoptosis, Autophagy, Cell Cycle, Cholesterol |
| UniProt ID | P23560 |
| NCBI Gene ID | 627 |
| Ensembl ID | ENSG00000176697 |
| OMIM | 113505 |
| GeneCards | BDNF |
| Human Protein Atlas | BDNF |
| Associated Diseases | Addiction, ADHD, aging, allergic airway inflammation, Als |
| Known Drugs/Compounds | acupuncture, aducanumab, ANTIDEPRESSANTS, BAICALEIN, Bifidobacterium bifidum CCFM1163, Bnt162B2 |
| Interactions | A2A receptor, A2A Receptor, ABCA7, ABETA, ACC, ACE |
| SciDEX Target | View Target Profile (4 clinical trials) |
| SciDEX Hypotheses | Hippocampal CA3-CA1 synaptic rescue via DHHC2-medi Hippocampal CA3-CA1 circuit rescue via neurogenesi Neuroplasticity-Enhanced Learning Hypothesis (+1 more) |
| KG Connections | 4736 knowledge graph edges |
| Databases | GeneCardsHPASTRING |
Knowledge base pages for this entity
graph TD
subgraph Signaling["Signaling"]
BDNF["BDNF"] -->|"activates"| TRKB["TRKB"]
BDNF["BDNF"] -->|"activates"| Als["Als"]
BDNF["BDNF"] -->|"activates"| Aging["Aging"]
BDNF["BDNF"] -->|"activates"| Stroke["Stroke"]
BDNF["BDNF"] -.->|"inhibits"| Als_1["Als"]
BDNF["BDNF"] -->|"activates"| Depression["Depression"]
BDNF["BDNF"] -->|"activates"| Synaptic_Plasticity["Synaptic Plasticity"]
BDNF["BDNF"] -->|"activates"| Neurogenesis["Neurogenesis"]
CREB["CREB"] -->|"activates"| BDNF["BDNF"]
TRKB_3["TRKB"] -->|"activates"| BDNF["BDNF"]
TNF["TNF"] -->|"activates"| BDNF["BDNF"]
EXERCISE["EXERCISE"] -->|"activates"| BDNF["BDNF"]
OXIDATIVE_STRESS["OXIDATIVE STRESS"] -->|"activates"| BDNF["BDNF"]
end
subgraph Pathology["Pathology"]
BDNF["BDNF"] -->|"associated with"| Als_2["Als"]
APP["APP"] -->|"associated with"| BDNF["BDNF"]
end
style BDNF fill:#4a1a6b,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0,font-weight:bold
style TRKB fill:#006494,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Als fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Aging fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Stroke fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Als_1 fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Depression fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Synaptic_Plasticity fill:#1b5e20,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Neurogenesis fill:#1b5e20,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Als_2 fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style CREB fill:#006494,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style TRKB_3 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style TNF fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style EXERCISE fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style APP fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style OXIDATIVE_STRESS fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0| Target | Relation | Type | Str |
|---|---|---|---|
| Neurogenesis | activates | pathway | 1.00 |
| TNF-Α | activates | gene | 1.00 |
| Als | associated_with | disease | 1.00 |
| NEURODEGENERATION | associated_with | gene | 1.00 |
| Inflammation | activates | disease | 1.00 |
| Differentiation | activates | pathway | 1.00 |
| DEPRESSION | therapeutic_target | gene | 1.00 |
| INFLAMMATION | activates | gene | 1.00 |
| Apoptosis | activates | pathway | 1.00 |
| Cancer | activates | disease | 1.00 |
| Neurodegeneration | associated_with | disease | 1.00 |
| Neurodegeneration | activates | disease | 1.00 |
| neurogenesis | activates | process | 1.00 |
| Als | inhibits | disease | 1.00 |
| Depression | therapeutic_target | disease | 1.00 |
| Als | regulates | disease | 1.00 |
| NEUROINFLAMMATION | activates | gene | 1.00 |
| Depression | regulates | disease | 1.00 |
| DEPRESSION | associated_with | gene | 1.00 |
| neurodegeneration | associated_with | disease | 1.00 |
| Neuroinflammation | activates | disease | 1.00 |
| PARKINSON'S DISEASE | associated_with | gene | 1.00 |
| Synaptic Plasticity | activates | pathway | 1.00 |
| Oxidative Stress | activates | pathway | 1.00 |
| HIPPOCAMPUS | associated_with | brain_region | 1.00 |
| Neurodegeneration | protects_against | disease | 1.00 |
| Als | activates | disease | 1.00 |
| Depression | activates | disease | 1.00 |
| Aging | activates | disease | 1.00 |
| Stroke | activates | disease | 1.00 |
| AKT | activates | gene | 1.00 |
| Alzheimer | activates | disease | 1.00 |
| Tumor | activates | disease | 1.00 |
| TRKB | activates | protein | 1.00 |
| Als | expressed_in | disease | 1.00 |
| Autophagy | activates | pathway | 1.00 |
| NEURODEGENERATIVE DISEASES | activates | gene | 1.00 |
| ALZHEIMER | activates | gene | 1.00 |
| GENES | activates | gene | 1.00 |
| TRKB | associated_with | gene | 1.00 |
| TAU | associated_with | gene | 0.98 |
| Depression | associated_with | disease | 0.95 |
| Cognitive Impairment | associated_with | phenotype | 0.95 |
| Alzheimer'S Disease | downregulates | disease | 0.95 |
| Neuronal Degeneration | inhibits | process | 0.95 |
| Alzheimer'S Disease | therapeutic_target | disease | 0.95 |
| Post-Traumatic Brain Injury | upregulates | disease | 0.95 |
| Neuroplasticity | promotes | process | 0.95 |
| thalamo-amygdala signaling | involved_in | pathway | 0.95 |
| Dendritic Complexity | promotes | phenotype | 0.95 |
| Source | Relation | Type | Str |
|---|---|---|---|
| entities-dna-methylation | interacts_with | wiki | 0.00 |
| NEURODEGENERATION | activates | gene | 1.00 |
| TRKB | activates | gene | 1.00 |
| exercise | activates | process | 1.00 |
| EXERCISE | activates | gene | 1.00 |
| AMYLOID | associated_with | protein | 1.00 |
| TNF | activates | gene | 1.00 |
| OXIDATIVE STRESS | activates | gene | 1.00 |
| CANCER | activates | gene | 1.00 |
| ALZHEIMER'S DISEASE | associated_with | disease | 1.00 |
| APOPTOSIS | associated_with | gene | 1.00 |
| CREB | activates | protein | 1.00 |
| APP | associated_with | gene | 1.00 |
| NEURODEGENERATION | protects_against | gene | 1.00 |
| Exercise | upregulates | process | 0.95 |
| Hypoxic preconditioning | upregulates | process | 0.95 |
| NPFF | upregulates | protein | 0.95 |
| Bnt162B2 | modulates | drug | 0.95 |
| Exercise Training | upregulates | process | 0.95 |
| Environmental Enrichment | upregulates | process | 0.95 |
| integrated stress response | activates | pathway | 0.92 |
| Butyrate | upregulates | compound | 0.90 |
| Quinolinic Acid | downregulates | compound | 0.90 |
| Stress | downregulates | process | 0.90 |
| HUNTINGTIN | transports | protein | 0.90 |
| CREB | regulates | protein | 0.90 |
| h-e0183502 | targets | hypothesis | 0.90 |
| Oxytocin | upregulates | drug | 0.90 |
| Regular exercise | upregulates | process | 0.90 |
| Cabergoline | upregulates | drug | 0.90 |
| h-856feb98 | targets | hypothesis | 0.90 |
| T-lymphocytes | produces | cell_type | 0.90 |
| Paeoniflorin | upregulates | compound | 0.90 |
| TDP-43 | associated_with | protein | 0.90 |
| microglial repopulation | contributes_to | phenotype | 0.90 |
| Huntington disease | inhibits | disease | 0.90 |
| h-47ab2be5 | targets | hypothesis | 0.90 |
| FNDC5 | upregulates | protein | 0.90 |
| dCas9-Tet1 | activates | protein | 0.90 |
| SORTILIN | regulates | protein | 0.90 |
| Optogenetic Stimulation | upregulates | mechanism | 0.90 |
| TDP-43 | regulates | protein | 0.90 |
| huntingtin | regulates | protein | 0.90 |
| SARM1 | regulates | gene | 0.90 |
| h-ee1df336 | targets | hypothesis | 0.90 |
| AKT | associated_with | gene | 0.90 |
| neuron | expressed_in | cell_type | 0.90 |
| h-var-9c0368bb70 | targets_gene | hypothesis | 0.90 |
| h-29ef94d5 | targets_gene | hypothesis | 0.90 |
| AAVT42 | transports | drug | 0.90 |
Hypotheses where this entity is a therapeutic target
| Hypothesis | Score | Disease | Analysis |
|---|---|---|---|
| Hippocampal CA3-CA1 synaptic rescue via DHHC2-mediated PSD95 | 0.861 | Alzheimer's disease | Circuit-level neural dynamics in neurode |
| Hippocampal CA3-CA1 circuit rescue via neurogenesis and syna | 0.820 | Alzheimer's disease | Circuit-level neural dynamics in neurode |
| Activity-Dependent Synaptic Tagging via CREB-BDNF-TrkB Signa | 0.610 | synaptic biology | What determines the selectivity of compl |
| Oxygen Pressure-Dependent BDNF Cascade: DHHC2/PSD95 Stabiliz | 0.580 | neurodegeneration | View |
| Neuroplasticity-Enhanced Learning Hypothesis | 0.566 | methodology | Unable to extract research questions - t |
| HBOT at 2.0 ATA for 60 min, 5x/week for 6 weeks enhances hip | 0.450 | neurodegeneration | What are the optimal oxygen pressure, du |
Scientific analyses that reference this entity
neurodegeneration | 2026-04-15 | 1 hypotheses Top: 0.740
neurodegeneration | 2026-04-14 | 2 hypotheses Top: 0.589
spatial memory | 2026-04-08 | 0 hypotheses
methodology | 2026-04-04 | 2 hypotheses Top: 0.566
neurodegeneration | 2026-04-04 | 9 hypotheses Top: 0.914
Experimental studies targeting or related to this entity
| Experiment | Type | Disease | Score | Feasibility | Model | Status | Est. Cost |
|---|---|---|---|---|---|---|---|
| Spp1 knockout prevents synaptic loss in AD mouse models | validation | Alzheimer's disease | 0.900 | 0.00 | Spp1 knockout AD mouse models | proposed | N/A |
| Synaptic plasticity and protein expression analysis in mPFC | exploratory | insomnia-anxiety comorbidity | 0.850 | 0.00 | mPFC brain slices from PCPA-tr | 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 |
| Exercise-BDNF-Mitophagy Biomarker Study in PD | clinical | Parkinson's Disease | 0.400 | 0.50 | human | proposed | $6,550,000 |
| 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 |
| Animal Model Comparison for Neurodegenerative Disease Therapeutics | clinical | Alzheimer's Disease | 0.400 | 0.50 | human | proposed | $7,100,000 |
| 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 |
Scientific publications cited in analyses involving this entity
| Title & PMID | Authors | Journal | Year | Citations |
|---|---|---|---|---|
| Antidepressant effects of combined eucommia-gastrodia extract via modulation of [PMID:41921863] | Xue L, Pan Z, Liu Y, Gan Q, Liu D, Liu D | Brain research bulletin | 2026 | 0 |
| Complementary mechanisms of high-carbohydrate diets and ketogenic diets restore [PMID:41475465] | Kwon H, Seo DS, Ahmad Y, Park S, Yoo J, | The Journal of nutritional bio | 2026 | 0 |
| TrkB promotes the neuronal secretion of soluble Siglec-2 (CD22) to mitigate micr [PMID:41922794] | Shi X, Cai SZ, Chai JL, Xu CY, Zhou BY, | Molecular psychiatry | 2026 | 0 |
| The Potential Functions and Beneficial Effects of Melatonin on Cognitive Impairm [PMID:41917799] | Li XY, Cheng YZ, Zhang YM, Hu F, Fang SK | Brain and behavior | 2026 | 0 |
| Biomarkers for Alzheimer's disease across diverse biological domains: an umbrell [PMID:40680830] | Kang J, Son Y, Yim Y, Cho H, Kim J et al | J Adv Res | 2026 | 0 |
| Nanotherapeutic potential of Baicalein-encapsulated hUC-MSC exosomes in Alzheime [PMID:41370943] | Xu J, He Z, Pan Y, Cao B, Chen G | Biomater Adv | 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 |
| Postbiotics and the gut-brain axis: A mechanistic review on modulating neuroinfl [PMID:41570486] | Lahariya R, Anand G, Kumari B, Priyadars | J Neuroimmunol | 2026 | 0 |
| miRNA-206 in muscle and central nervous system crosstalk during exercise: A doub [PMID:41571168] | Malvandi AM, Gerosa L, Maroni P, Orlando | Neurosci Biobehav Rev | 2026 | 0 |
| Experts' narrative review "Mastication, Hippocampal Structure Changes and Cognit [PMID:41576846] | Piancino MG | Arch Oral Biol | 2026 | 0 |
| Plant-derived bioactive compounds modulate the gut microbiota in Alzheimer's dis [PMID:41678917] | Xue D, Hu X, Li R, Sun T, Qian S et al. | Phytomedicine | 2026 | 0 |
| Dysregulation of Drp1 and Mfn2 is associated with reduced PSD-95, synaptophysin, [PMID:41932483] | Alfateh M, Vasconcelos C, Choker AH, Moh | Int J Biol Macromol | 2026 | 0 |
| AICAR improves depression-like behaviors and is associated with hippocampal AMPK [PMID:41932583] | Takahashi K, Kurokawa K, Kawaguchi R, Ta | Neurochem Int | 2026 | 0 |
| Human umbilical cord mesenchymal stem cells therapy for Alzheimer's disease: a s [PMID:41847685] | Si C, Ma L, Ding W, Tian Y, Zhang J, Cao | Frontiers in neurology | 2026 | 0 |
| Cannabidiol and pBDNF Cotreatment Attenuates Pathological Symptoms and Improves [PMID:41924980] | Chaulagain B, Gothwal A, Mahanta AK, Jar | ACS chemical neuroscience | 2026 | 0 |
| Advances and Therapeutic Potential of Anthraquinone Compounds in Neurodegenerati [PMID:41868184] | Liu Z, Zhang H, Wan B, Yin S, Yue R | Drug design, development and t | 2026 | 0 |
| Modulation of mitochondrial quality by exercise mimetics: A potential strategy f [PMID:41804756] | Ke Z, Wang B, Liang R | Journal of Alzheimer's disease | 2026 | 0 |
| Neurotransmitter dysregulation in depression, anxiety, and suicidality: From syn [PMID:41924767] | K S V ABG, Verma AK, A SS, Sinha SS, Boy | Psychiatry research | 2026 | 0 |
| Hippocampal neural circuit mechanisms in Alzheimer's disease revealed by viral-g [PMID:41082949] | ["Ye Q", "Gast G", "Holmes T", "Xu X"] | Neurobiology of disease | 2025 | 0 |
| Therapeutic Potential of Natural Compounds for Brain Ischemia-Reperfusion Injury [PMID:41007298] | ["Yoo K", "Won M", "Ahn J", "Park J"] | Biology | 2025 | 0 |
Multi-agent debates referencing this entity
closed · Rounds: 4 · Score: 0.71 · 2026-04-16
closed · Rounds: 4 · Score: 0.95 · 2026-04-15
closed · Rounds: 4 · Score: 0.95 · 2026-04-13
closed · Rounds: 4 · Score: 0.95 · 2026-04-10
closed · Rounds: 4 · Score: 0.95 · 2026-04-10
closed · Rounds: 4 · Score: 0.95 · 2026-04-09
closed · Rounds: 4 · Score: 0.95 · 2026-04-06
closed · Rounds: 4 · Score: 0.91 · 2026-04-06
closed · Rounds: 4 · Score: 0.95 · 2026-04-06
closed · Rounds: 4 · Score: 0.93 · 2026-04-06
Hypotheses and analyses mentioning BDNF in their description or question text