LRRK2 G2019S regulation of clusterin and impaired astrocyte uptake of alpha-synuclein fibrils

neurodegeneration resolved composite 67%
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Composite
67%
Novelty
78%
Mechanistic
—
Druggability
—
Priority
65%
Importance
70%
Tractability
60%
Market price
50%

Description

PMID:40355981 showed LRRK2 G2019S astrocytes have impaired alpha-synuclein fibril ingestion due to dysregulated clusterin. However, the mechanism by which LRRK2 G2019S regulates clusterin expression, whether restoring clusterin rescues alpha-syn clearance, and whether this pathway contributes to human PD progression are unknown.

Evidence summary

Resolved by hypothesis h-var-08a4d5c07a: Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming in Neurodegeneration. Score: 0.907. Supporting PMIDs: 33875891, 30610225, 31748742, 27519954, 33741860.

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