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How does IGF2BP1 mechanistically regulate Keap1/Nrf2 signaling through m6A modifications?

OPEN

The study identifies IGF2BP1 as an m6A reader that regulates Keap1/Nrf2 pathway activity, but the specific molecular mechanism linking m6A binding to pathway modulation remains unexplained. Understanding this mechanism is crucial for developing targeted therapeutic interventions. Gap type: unexplained_observation Source paper: IGF2BP1 exacerbates neuroinflammation and cerebral ischemia/reperfusion injury by regulating neuronal ferroptosis and microglial polarization. (2025, Biochimica et biophysica acta. Molecular basis of disease, PMID:40294852)

Priority: 0.80 Domain: neuroinflammation Hypotheses: 0
📊 Landscape Analysis

Landscape Summary: How does IGF2BP1 mechanistically regulate Keap1/Nrf2 signaling through m6A modifications? is a 0.8 priority gap in neuroinflammation. It has 0 linked hypotheses with average composite score 0.000. Status: open.

Key Unanswered Questions

Key Researchers

Colonna, Sevlever, et al. (TREM2 biology)

Clinical Trials

How does IGF2BP1 mechanistically regulate Keap1/Nrf2 signaling through m6A modifications? — INVOKE-2 (completed)

📈 Living Dashboards
0
Hypotheses
0.000
Top Score
0.000
Avg Score
0
Debates
0.00
Avg Quality
0%
Resolution
0
Mechanistic Families
Gap Resolution Progress0%

Hypothesis Score Distribution

🏆 Competing Hypotheses (Ranked by Score)

No hypotheses linked to this gap yet.

🌊 Knowledge Graph Connections

activates (7)

melatonin→Nrf2Isoliquiritigenin→Nrf2Nrf2→Antioxidant Responsekaempferol→Nrf2P62→Nrf2
▸ Show 2 more

binds (4)

IGF2BP1→N6-MethyladenosineNRF2→Keap1IGF2BP1→m6A ModificationIGF2BP1→Neurodevelopmental Mrnas

causes (1)

Nrf2→Hepatomegaly

contributes to (4)

Nrf2→GlycogenosisNrf2→Hepatocyte HyperplasiaNrf2→SteatosisIGF2BP1→Neural Fate Specification

counteracts (1)

41101499→Nrf2

counteracts the effects of (1)

41101499→Nrf2

downregulates (1)

IFNΓ→Nrf2

inhibits (1)

KEAP1→Nrf2

interacts with (4)

Nrf2→SQSTM1SQSTM1→Nrf2AMPK→Nrf2IGF2BP1→SYNCRIP

involved in (5)

IGF2BP1→Neural Progenitor Temporal PatterningIGF2BP1→Neural Progenitor PatterningIGF2BP1→Larval Brain DevelopmentIGF2BP1→Neural Diversity GenerationIGF2BP1→Neural Fate Specification

maintains (1)

41684011→Nrf2

modulates (1)

Nrf2→Mitophagy

promotes nuclear translocation of (1)

41460594→Nrf2

regulates (6)

IGF2BP1→Temporal Regulators41684011→Nrf2Nrf2→autophagy27143001→Nrf2IGF2BP1→Temporal Neural Fate Specification
▸ Show 1 more

suppresses (3)

Nrf2→FerroptosisNrf2→OXIDATIVE STRESSJNK→Nrf2

targets (2)

GENISTEIN→Nrf2EPIGALLOCATECHIN GALLATE→Nrf2

upregulates (5)

Nrf2→PDGFNrf2→EGFNrf2→Antioxidant EnzymesAMPK/SIRT1 Signaling Pathway→Nrf2IFNΓ→Keap1

upstream of (2)

Nrf2→PINK1/Parkin axisNrf2→PINK1
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