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GBA-alpha-synuclein bidirectional loop in Parkinson's

PARTIALLY ADDRESSED

GBA mutations impair lysosomal function and promote alpha-synuclein aggregation, but alpha-synuclein itself inhibits GBA activity. The therapeutic implications of breaking this loop at different points remain unclear.

Priority: 0.88 Domain: neurodegeneration Hypotheses: 3
📊 Landscape Analysis

Landscape Summary: GBA-alpha-synuclein bidirectional loop in Parkinson's is a 0.88 priority gap in neurodegeneration. It has 3 linked hypotheses with average composite score 0.000. Status: partially_addressed.

Key Unanswered Questions

Key Researchers

Colonna, Sevlever, et al. (TREM2 biology)

Clinical Trials

GBA-alpha-synuclein bidirectional loop in Parkinson's — INVOKE-2 (completed)

📈 Living Dashboards
3
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)
Mitochondrial-Lysosomal Contact Site Modulators
Target: VDAC1 + LAMP1 Pathway: N/A
0.000
score
CRISPR-dCas9 Epigenetic Reprogramming of Stress Granules
Target: TDP43 + FUS Pathway: N/A
0.000
score
Selective Glucosylceramide Synthase Inhibition with Lysosomal Enhancem
Target: UGCG + TFEB Pathway: N/A
0.000
score
Temporal Metabolic Rewiring with Circadian Modulators
Target: NR1D1 + CLOCK + TFEB Pathway: N/A
0.000
score
Pharmacological Chaperone-Mediated Selective Autophagy
Target: GBA + SQSTM1 Pathway: N/A
0.000
score
Engineered Extracellular Vesicle Therapy with Synthetic Biology
Target: GBA + HSP70 + LAMP2A Pathway: N/A
0.000
score
Lipid Raft Disruptors with Membrane Fluidizers
Target: GBA + SNCA Pathway: N/A
0.000
score
🌊 Knowledge Graph Connections

activates (19)

UBIQUITIN→ParkinsonPARKINSON'S DISEASE→ParkinsonPARKIN→ParkinsonParkinson→Apoptosis6-OHDA→Parkinson
▸ Show 14 more

associated with (7)

UBIQUITIN→ParkinsonParkinson→FerroptosisNeuroinflammation→ParkinsonParkinson→Amyotrophic Lateral SclerosisCancer→Parkinson
▸ Show 2 more

causes (1)

LRRK2→Parkinson

regulates (7)

NEURODEGENERATIVE DISORDERS→ParkinsonParkinson→AutophagyPINK1→ParkinsonPARKIN→ParkinsonAMYOTROPHIC LATERAL SCLEROSIS→Parkinson
▸ Show 2 more

therapeutic target (16)

PARKINSON'S DISEASE→ParkinsonDNA→ParkinsonAUTOPHAGY→ParkinsonAKT→ParkinsonParkinson→Proteasome
▸ Show 11 more
🕑 Activity Feed
📈 Mitochondrial-Lysosomal Contact Site Modulators score=0.000 2026-04-28T21:58
📈 CRISPR-dCas9 Epigenetic Reprogramming of Stress Granules score=0.000 2026-04-28T21:58
📈 Selective Glucosylceramide Synthase Inhibition with Lysosoma score=0.000 2026-04-28T21:58
📈 Temporal Metabolic Rewiring with Circadian Modulators score=0.000 2026-04-28T21:58
📈 Pharmacological Chaperone-Mediated Selective Autophagy score=0.000 2026-04-28T21:58
💬 Discussion

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