What determines the GPX4/ACSL4 balance that switches microglia from protective to ferroptotic states?

PARTIALLY ADDRESSED

While ACSL4-driven ferroptosis was strongly supported, the molecular triggers that tip the balance from protective GPX4 activity to pathological ACSL4-mediated vulnerability remain unclear. This balance point could be a critical therapeutic target. Source: Debate session sess_SDA-2026-04-02-gap-seaad-v4-20260402065846 (Analysis: SDA-2026-04-02-gap-seaad-v4-20260402065846)

Priority: 0.88 Domain: immunology Hypotheses: 0

📊 Landscape Analysis

Landscape Summary: What determines the GPX4/ACSL4 balance that switches microglia from protective to ferroptotic states? is a 0.88 priority gap in immunology. It has 0 linked hypotheses with average composite score 0.000. Status: partially_addressed.

Key Unanswered Questions

What is the optimal TREM2 modulation strategy across disease stages?
How does DAM activation state affect therapeutic outcomes?
What biomarkers predict response to TREM2-targeted interventions?

Key Researchers

Colonna, Sevlever, et al. (TREM2 biology)

Clinical Trials

What determines the GPX4/ACSL4 balance that switches microglia from protective to ferroptotic states? — INVOKE-2 (completed)

📈 Living Dashboards

0

Hypotheses

0.000

Top Score

0.000

Avg Score

0

Debates

0.00

Avg Quality

60%

Resolution

0

Mechanistic Families

Gap Resolution Progress60%

Hypothesis Score Distribution

🏆 Competing Hypotheses (Ranked by Score)

No hypotheses linked to this gap yet.

🌊 Knowledge Graph Connections

NULL (1)

GPX4→ferroptosis

activates (13)

ACSL4→FERROPTOSISGPX4→NRF2GPX4→FerroptosisGPX4→CANCERGPX4→FERROPTOSIS

▸ Show 8 more

GPX4→ROSGPX4→STINGGPX4→CancerSLC7A11→GPX4GPX4→AlsGPX4→TumorGPX4→Oxidative StressGPX4→Inflammation

associated with (1)

HNRNPA2B1→GPX4

binds to (1)

describes (1)

genes-acsl4→ACSL4

downregulates (3)

MIR130B→ACSL4Emodin→GPX4Rotenone→GPX4

encodes (2)

ACSL4→ACSL4GPX4→GPX4

inhibits (11)

GPX4→CancerGPX4→ferroptosisGPX4→FerroptosisGPX4→ROSGPX4→NRF2

▸ Show 6 more

GPX4→TumorGPX4→FERROPTOSISSLC7A11→GPX4GPX4→AlsGPX4→CANCERMIR130B→ACSL4

interacts with (1)

mediates (1)

ACSL4→Ferroptosis

regulates (9)

GPX4→FerroptosisTMEM16F→ACSL4GPX4→CancerSLC7A11→GPX4GPX4→FERROPTOSIS

▸ Show 4 more

GPX4→CANCERGPX4→AlsTMEM16F→GPX4GPX4→Oxidative Stress

targets (1)

therapeutic target (3)

GPX4→CancerGPX4→TumorGPX4→CANCER

upregulates (2)

NRF2→GPX4Lactoferrin→GPX4

🕑 Activity Feed

✏ update on knowledge_gap by None 2026-04-25T22:15

✏ update on knowledge_gap by None 2026-04-15T23:43

✏ update on knowledge_gap by None 2026-04-15T23:43

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