Lutein inhibits ATF3-mediated PINK1/Parkin signaling to modulate neuronal mitophagy and alleviate Parkinson's disease progression.

BACKGROUND AND PURPOSE: Mitophagy impairment plays a key role in Parkinson's disease (PD) progression. Our previous studies showed that lutein, a carotenoid, alleviates PD by inhibiting neuronal ferroptosis and microglial pro-inflammatory polarization. However, whether lutein regulates mitophagy in PD remains unclear. This study investigates the effects and molecular mechanisms of lutein on mitophagy in PD neuronal cells. METHODS: promoter. RESULTS: to negatively modulate its transcription. Knockdown of PINK1 reverses the mitophagy activation and neuroprotective effects induced by ATF3 silencing. CONCLUSION: Lutein downregulates ATF3, thereby relieving its repression of the PINK1/Parkin signaling pathway and supporting mitochondrial quality control and mitophagy-associated signaling, which slows PD progression.