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Astrocyte-Intrinsic NLRP3 Inflammasome Activation by Alpha-Synuclein Aggregates Drives Non-Cell-Autonomous Neurodegeneration

h-var-adfecef68a
## Molecular Mechanism and Rationale The NLRP3 inflammasome pathway in astrocytes represents a critical neuroinflammatory cascade initiated by alpha-synuclein (α-Syn) aggregate recognition and subsequent intracellular danger signal processing. Extracellular α-Syn fibrils bind to astrocytic Toll-like receptor 2 (TLR2) and CD44 surface receptors, triggering MyD88-dependent NF-κB activation that con

Elo ratings (across arenas)

ArenaRatingRDW-L-DN
loop:loop-43530d9a960b 1713 ±275 1-0-0 1
neurodegeneration 1511 ±99 8-12-0 20
global 1394 ±139 4-6-0 10

Ancestry (oldest → this)

mutate · gen 2
parent: h-e7e1f943
Restricts the inflammasome effector scope from peripheral microbial/gut-brain axis to CNS-intrinsic astrocytes, and substitutes microbial PAMPs with alpha-synuclein protein aggregates as the upstream

Descendants

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