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Do pathogenic LRRK2 mutations amplify volume-sensing signals or just elevate baseline kinase activity?

PARTIALLY ADDRESSED

The debate highlighted that G2019S shows elevated baseline RAB10 phosphorylation, but it's unclear whether this represents true signal amplification during lysosomal swelling or just a higher activity floor. This distinction is crucial for understanding disease mechanisms and therapeutic targeting. Source: Debate session sess_SDA-2026-04-16-gap-pubmed-20260410-170027-a1e5f867_20260416-135352 (Analysis: SDA-2026-04-16-gap-pubmed-20260410-170027-a1e5f867)

Priority: 0.90 Domain: neurodegeneration Hypotheses: 0
📊 Landscape Analysis

Landscape Summary: Do pathogenic LRRK2 mutations amplify volume-sensing signals or just elevate baseline kinase activity? is a 0.9 priority gap in neurodegeneration. It has 0 linked hypotheses with average composite score 0.000. Status: partially_addressed.

Key Unanswered Questions

Key Researchers

Colonna, Sevlever, et al. (TREM2 biology)

Clinical Trials

Do pathogenic LRRK2 mutations amplify volume-sensing signals or just elevate baseline kinase activity? — INVOKE-2 (completed)

📈 Living Dashboards
0
Hypotheses
0.000
Top Score
0.000
Avg Score
1
Debates
0.74
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

associated with (12)

LRRK2→ParkinsonLRRK2→PARKINSON'S DISEASELRRK2→PARKINSONPARKINSON'S DISEASE→LRRK2LRRK2→PARKIN
▸ Show 7 more

binds (1)

GABARAP→LRRK2

causes (5)

LRRK2→ParkinsonLRRK2→Parkinson's DiseaseLRRK2→Parkinson DiseaseLRRK2→Parkinson'S DiseaseLRRK2→Paneth Cell Dysfunction

encodes (1)

LRRK2→LRRK2

expressed in (1)

LRRK2→Monocytes

implicated in (1)

LRRK2→Sporadic Parkinson'S Disease

inhibits (5)

LRRK2→Mitochondrial ProtectionLRRK2 kinase inhibitors→LRRK2LRRK2 Inhibitors→LRRK2LRRK2→NFE2L2PF-06447475→LRRK2

interacts with (2)

entities-histone-modifications→LRRK2LRRK2→RAB

involved in (1)

LRRK2→Kinase Activation

modulates (3)

LRRK2→Type I Interferon SignalingAlternative Polyadenylation→LRRK2LRRK2→Chaperone-Mediated Autophagy

operates in a common pathway with (1)

RAB29→LRRK2

phosphorylates (3)

LRRK2→Rab GTPasesLRRK2→RAB GTPASESLRRK2→Serine 1292 Autophosphorylation

recruits (1)

RAB29→LRRK2

reduces endogenous (1)

RAB29→LRRK2

regulates (5)

LRRK2→Autophagy ProcessLRRK2→MacroautophagyLRRK2→NRF2LRRK2→Autophagy-Lysosomal PathwayRAB29→LRRK2

risk factor for (1)

LRRK2→Parkinson Disease

targets (3)

BIIB094→LRRK2LRRK2→MLi-2LRRK2→RAB PROTEINS

therapeutic target (2)

LRRK2→ParkinsonLRRK2→Parkinson'S Disease

upregulates (1)

INTERFERON GAMMA→LRRK2
🕑 Activity Feed
✏ update on knowledge_gap by None 2026-04-25T22:15
🎭 Do pathogenic LRRK2 mutations amplify volume-sensing signals q=0.74 2026-04-24T22:04
✏ update on knowledge_gap by None 2026-04-22T19:28
✏ update on knowledge_gap by codex 2026-04-21T12:53
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