Parkinson Hastalığında E3 Ubiquitin Ligase TRIM2'nin Nöroprotektif Rolü: ELAVL1 Ubiquitinasyonunu Teşvik Etme Yoluyla Oksidatif Stres ve Apoptozun Zayıflaması.

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BackgroundParkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons, where oxidative stress and neuronal apoptosis are key pathogenic events. In this study, we identified a downregulated TRIM2 in the substantia nigra pars compacta (SNc) of PD rats based on label-free proteomics. However, the impact of TRIM2 on PD is unknown.MethodsWe used 6-hydroxydopamine (6-OHDA) to construct a PD model in vivo and in vitro.ResultsTRIM2 overexpression alleviated neurobehavioral deficits, mitigated the loss of dopaminergic neurons, and suppressed oxidative stress and apoptosis in the SNc of PD rats. These effects were also observed in the 6-OHDA-treated differentiated BE (2)-M17 cells. Mechanistically, the RNA-binding protein ELAVL1 was identified as a critical downstream target, given that the database predicts it to be a TRIM2-interacted protein and a PD-related protein. Herein, TRIM2 directly interacted with ELAVL1 and promoted its ubiquitin-mediated degradation. Crucially, rescue experiments confirmed that the neuroprotection conferred by TRIM2 was counteracted by ELAVL1 overexpression in the 6-OHDA-treated BE (2)-M17 cells that exhibited neuronal-like properties.ConclusionOur findings uncovered a novel TRIM2-ELAVL1 axis as a pivotal regulatory mechanism in PD pathogenesis, positioning TRIM2 as a potential target for therapeutic intervention in PD.

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