LRRK2 Haploinsufficiency Traps Microglia in Senescence-Like Pro-Inflammatory State Accelerating Alpha-Synuclein Pathology in Parkinson's Disease

h-analogy-b8828d7f

Analogous to ALS-associated TBK1 loss trapping microglia in SASP, LRRK2 haploinsufficiency (common in PD patients carrying G2019S or other risk variants) may lock microglia into a senescent transcriptional state characterized by chronic pro-inflammatory cytokine secretion. This SASP-like microglial environment would potentiate alpha-synuclein aggregation and impair clearance, accelerating dopamine