MAPK
Entity Detail — Knowledge Graph Node
Understanding Entity Pages
This page aggregates everything SciDEX knows about MAPK: 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.
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Regenerate portrait ↻| Gene Symbol | MAPK |
| Synaptic plasticity | ERK activation is required for long-term potentiation (LTP) and memory consolidation through phosphorylation of CREB, Elk-1, and MSK1 transcription factors. [@thomas2004] |
| Neuronal survival | ERK phosphorylates and inactivates the pro-apoptotic BCL-2 family member BAD, promotes expression of anti-apoptotic proteins, and activates the RSK→CREB survival pathway |
| Neurite outgrowth | Sustained ERK activation drives neuronal differentiation through transcriptional programs distinct from those activated by transient ERK signals |
| Neuroinflammation | p38α drives transcription and stabilization of pro-inflammatory cytokine mRNAs in microglia. It is essential for NF-κB-dependent transcription of IL-6, TNF-α, IL-1β, and iNOS. [@lee2017] |
| Tau phosphorylation | JNK phosphorylates tau at multiple epitopes and promotes neurofibrillary tangle formation |
| Synaptic dysfunction | p38 activation in dendritic spines promotes AMPA receptor endocytosis and long-term depression (LTD), contributing to synaptic weakening |
| Microglial activation | p38α is the dominant isoform mediating classical (M1) microglial activation, phagocytosis, and cytokine production |
| Axonal degeneration | The DLK→MKK4→JNK pathway is a master regulator of Wallerian degeneration and axonal injury signaling |
| APP processing | JNK activation increases APP phosphorylation at Thr668, promoting amyloidogenic processing and Aβ production |
| JNK in dopaminergic death | JNK activation by oxidative stress (6-OHDA, MPTP) and LRRK2 gain-of-function mutations triggers c-Jun-dependent apoptosis in substantia nigra pars compacta neurons |
| ERK in neuroprotection | GDNF and BDNF signaling through ERK is neuroprotective for dopaminergic neurons; loss of ERK signaling contributes to neuronal vulnerability |
| p38 in motor neurons | p38 activation is an early event in SOD1-G93A mouse motor neurons, preceding symptom onset. p38 promotes phosphorylation of neurofilaments (NEFL, NEFH), disrupting axonal transport. [@dewil2007] |
| ASK1-p38 axis | Apoptosis signal-regulating kinase 1 (ASK1) is activated by oxidative stress and mutant SOD1, triggering the p38 and JNK cascades in motor neurons |
| DLK-JNK in axonal degeneration | The dual leucine zipper kinase (DLK) → MKK4 → JNK pathway drives axonal degeneration in ALS models; DLK inhibition prolongs survival in SOD1 mutant mice |
| Associated Diseases | Aging, Als, Alzheimer, Alzheimer's disease |
| Known Drugs/Compounds | 116B, ANTIOXIDANTS, berberine, BRAF inhibitors, CHOLIX, CSA |
| Interactions | ACAT1, ACHE, Actin, AD, ADAM10, ADORA2A |
| KG Connections | 3280 knowledge graph edges |
| Databases | GeneCardsUniProtNCBI GeneHPASTRING |
Wiki Pages (21)
Knowledge base pages for this entity
MAPK Signaling Pathways in Neurodegeneration
mechanism · 1665 wordsMAPK9 Gene
gene · 3305 wordsMAPK/ERK Signaling Pathway in Neurodegeneration
mechanism · 3210 wordsJNK/p38 MAPK Signaling Pathway in Neurodegeneration
mechanism · 2736 wordsJNK/p38 MAPK Inhibitor Companies for Parkinson's Disease
company · 2217 wordsMAPK4 Gene
gene · 1718 wordsPathway Diagram
graph TD
MAPK["MAPK"]
Neurodegeneration{"Neurodegeneration"}
MAPK -->|"involved_in"| Neurodegeneration
mTOR(["mTOR"])
MAPK -->|"regulates"| mTOR
mitophagy["mitophagy"]
MAPK -->|"regulates"| mitophagy
type_2_diabetes_mellitus{"type 2 diabetes mellitus"}
MAPK -->|"associated_with"| type_2_diabetes_mellitus
Alzheimer_s_disease{"Alzheimer's disease"}
MAPK -->|"associated_with"| Alzheimer_s_disease
STAT3(["STAT3"])
MAPK -->|"activates"| STAT3
LPS["["LPS"]]
LPS -->|"activates"| MAPK
gallic_acid["["gallic acid"]]
gallic_acid -.->|"inhibits"| MAPK
paeoniflorin["["paeoniflorin"]]
paeoniflorin -.->|"inhibits"| MAPK
ginseng_root_extract["["ginseng root extract"]]
ginseng_root_extract -.->|"inhibits"| MAPK
style MAPK fill:#1a3a4a,stroke:#ce93d8,stroke-width:3px,color:#e0e0e0Outgoing (2001)
| Target | Relation | Type | Str |
|---|---|---|---|
| gastric cancer | associated_with | disease | 0.95 |
| cellular proliferation | regulates | process | 0.90 |
| colitis-associated colorectal cancer | associated_with | disease | 0.90 |
| NF-kB signaling | participates_in | pathway | 0.90 |
| TDP-43 | phosphorylates | protein | 0.90 |
| metastasis | promotes | process | 0.90 |
| ubiquitin-proteasome | participates_in | pathway | 0.90 |
| ADIPOR1 | activates | protein | 0.90 |
| ATF2 | upstream_of | protein | 0.90 |
| liver fibrosis | associated_with | disease | 0.90 |
| DRP1 | phosphorylates | protein | 0.90 |
| LCH | drives | disease | 0.90 |
| cell migration | regulates | process | 0.90 |
| Senescent Myeloid Cells | causes | cell_type | 0.90 |
| neurons | expressed_in | cell_type | 0.90 |
| PI3K-AKT-mTOR signaling | participates_in | pathway | 0.90 |
| Tumor Growth | associated_with | phenotype | 0.90 |
| Mitochondrial Fragmentation | causes | process | 0.90 |
| neuroinflammation | inhibits | disease | 0.90 |
| unfolded protein response | participates_in | pathway | 0.90 |
| Mitochondrial Fission | activates | process | 0.90 |
| oxidative stress response | participates_in | pathway | 0.90 |
| MAPK signaling | participates_in | pathway | 0.90 |
| inflammatory cytokine secretion | promotes | process | 0.88 |
| oxidative stress | promotes | process | 0.88 |
| neuroinflammation | regulates | process | 0.86 |
| Neurodegeneration | associated_with | disease | 0.85 |
| microglia activation | activates | process | 0.85 |
| cholangiocarcinoma | therapeutic_target | disease | 0.85 |
| cell survival | promotes | process | 0.85 |
| PILOCYTIC ASTROCYTOMAS | involved_in | entity | 0.85 |
| microglia | expressed_in | cell_type | 0.85 |
| Lithium Neurotoxicity | involved_in | process | 0.85 |
| microglia activation | regulates | process | 0.85 |
| microglia | associated_with | cell_type | 0.85 |
| Inflammation | activates | process | 0.85 |
| Pyroptosis | activates | process | 0.85 |
| inflammation | drives | process | 0.85 |
| Inflammatory Cytokine Secretion | activates | process | 0.85 |
| MAPK | encodes | protein | 0.85 |
| Inflammatory Cytokine Expression | regulates | process | 0.85 |
| astrocyte activation | activates | process | 0.83 |
| Alzheimer's disease | associated_with | disease | 0.82 |
| mitochondrial dysfunction | regulates | process | 0.80 |
| KIAA1549::BRAF | associated_with | protein | 0.80 |
| multiple sclerosis | therapeutic_target | disease | 0.80 |
| mTOR | regulates | protein | 0.80 |
| Parkinson's disease | implicated_in | disease | 0.80 |
| INFLAMMATORY MEDIATORS | regulates_production_of | protein | 0.80 |
| APOPTOSIS | associated_with | process | 0.80 |
Incoming (3678)
| Source | Relation | Type | Str |
|---|---|---|---|
| INFLAMMATION | activates | gene | 1.00 |
| ROS | activates | gene | 1.00 |
| TNF | activates | gene | 1.00 |
| P38 | therapeutic_target | gene | 1.00 |
| TNF-Α | activates | gene | 1.00 |
| Inflammation | activates | disease | 1.00 |
| NF-KB | associated_with | protein | 1.00 |
| CYTOKINES | activates | gene | 1.00 |
| Inflammation | therapeutic_target | disease | 1.00 |
| TNF | therapeutic_target | gene | 1.00 |
| MTOR | activates | gene | 1.00 |
| AKT | associated_with | gene | 1.00 |
| CANCER | associated_with | gene | 1.00 |
| APOPTOSIS | therapeutic_target | gene | 1.00 |
| APOPTOSIS | regulates | gene | 1.00 |
| JNK | activates | gene | 1.00 |
| MITOCHONDRIA | activates | gene | 1.00 |
| NEUROINFLAMMATION | activates | gene | 1.00 |
| AKT | therapeutic_target | gene | 1.00 |
| TNF-Α | inhibits | gene | 1.00 |
| AMYLOID | associated_with | protein | 1.00 |
| PI3K | therapeutic_target | gene | 1.00 |
| Cancer | therapeutic_target | disease | 1.00 |
| ERK | inhibits | gene | 1.00 |
| AUTOPHAGY | regulates | gene | 1.00 |
| ALZHEIMER'S DISEASE | associated_with | disease | 1.00 |
| AKT | inhibits | gene | 1.00 |
| ERK1 | activates | gene | 1.00 |
| CANCER | inhibits | gene | 1.00 |
| P38 | inhibits | gene | 1.00 |
| IL-6 | activates | gene | 1.00 |
| Carcinoma | activates | disease | 1.00 |
| ERK | activates | gene | 1.00 |
| TNF | inhibits | gene | 1.00 |
| NF-ΚB | inhibits | gene | 1.00 |
| MTOR | regulates | gene | 1.00 |
| Cancer | inhibits | disease | 1.00 |
| Cancer | associated_with | disease | 1.00 |
| Als | inhibits | disease | 1.00 |
| Cancer | activates | disease | 1.00 |
| AUTOPHAGY | activates | gene | 1.00 |
| Tumor | activates | disease | 1.00 |
| AKT | activates | gene | 1.00 |
| JNK | inhibits | gene | 1.00 |
| P38 | activates | gene | 1.00 |
| NEURODEGENERATION | activates | gene | 1.00 |
| ERK | therapeutic_target | gene | 1.00 |
| Inflammation | regulates | disease | 1.00 |
| CANCER | therapeutic_target | gene | 1.00 |
| PI3K | associated_with | gene | 1.00 |
Targeting Hypotheses (2)
Hypotheses where this entity is a therapeutic target
| Hypothesis | Score | Disease | Analysis |
|---|---|---|---|
| DLK MAPK Pathway Inhibition to Block Tau-Induced Neurotoxici | 0.634 | neurodegeneration | Should microtubule-stabilizing drugs be |
| Astrocyte CD38-erk Mapk signaling controls mitochondrial tra | 0.380 | ALS and Alzheimer's disease | Mitochondrial transfer between neurons a |
Mentioning Analyses (9)
Scientific analyses that reference this entity
Neuroinflammation and microglial priming in early AD
neurodegeneration | 2026-04-04 | 7 hypotheses Top: 0.710
Tau propagation mechanisms and therapeutic interception points
neurodegeneration | 2026-04-04 | 15 hypotheses Top: 0.814
SEA-AD Single-Cell Analysis: Cell-Type Vulnerability in Alzheimer's Disease
neurodegeneration | 2026-04-04 | 5 hypotheses Top: 0.649
Gene expression changes in aging mouse brain predicting neurodegenerative vulner
neurodegeneration | 2026-04-03 | 43 hypotheses Top: 0.893
Circuit-level neural dynamics in neurodegeneration
neuroscience | 2026-04-03 | 70 hypotheses Top: 0.964
Experiments (0)
Experimental studies targeting or related to this entity
| Experiment | Type | Disease | Score | Feasibility | Model | Status | Est. Cost |
|---|---|---|---|---|---|---|---|
| No experiments found | |||||||
Related Papers (0)
Scientific publications cited in analyses involving this entity
| Title & PMID | Authors | Journal | Year | Citations |
|---|---|---|---|---|
| No papers found | ||||
Debates (20)
Multi-agent debates referencing this entity
Extended debate: Closed-loop transcranial focused ultrasound with 40Hz gamma ent
closed · Rounds: 6 · Score: 0.95 · 2026-04-27
Extended debate: Closed-loop tACS targeting EC-II SST interneurons to block tau
closed · Rounds: 6 · Score: 0.95 · 2026-04-27
Debate: Closed-loop transcranial focused ultrasound targeting entorhinal PV inte
closed · Rounds: 4 · Score: 0.65 · 2026-04-27
Debate: Closed-loop tACS targeting EC-II SST interneurons to block tau propagati
closed · Rounds: 4 · Score: 0.71 · 2026-04-27
Debate: Closed-loop transcranial focused ultrasound to restore hippocampal gamma
closed · Rounds: 4 · Score: 0.87 · 2026-04-27
Debate: Closed-loop tACS targeting EC-II PV interneurons to suppress burst firin
closed · Rounds: 4 · Score: 0.48 · 2026-04-27
Debate: Closed-loop tACS targeting EC-II somatostatin interneurons to restore de
closed · Rounds: 4 · Score: 0.54 · 2026-04-27
Debate: Microglial TREM2 downregulation impairs damage-associated response in la
closed · Rounds: 4 · Score: 0.21 · 2026-04-27
Debate: Closed-loop transcranial focused ultrasound with real-time gamma feedbac
closed · Rounds: 4 · Score: 0.19 · 2026-04-27
Hypothesis debate: Closed-loop transcranial alternating current stimulation to r
closed · Rounds: 4 · Score: 0.40 · 2026-04-27
Related Research
Hypotheses and analyses mentioning MAPK in their description or question text
No additional research found