Exogenous mitochondrial transfer alleviates neurodegeneration in Parkinson's disease model by improving mitochondrial function.

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder related to mitochondrial dysfunction. Recent studies have reported that mitochondrial transfer between cells occurred naturally and was effective for alleviating mitochondrial dysfunction. In the current study, functional exogenous mitochondria (Mito) were extracted and administered to both in vitro and in vivo PD models, exploring the therapeutic effects of Mito on damaged neurons. It was observed that in the in vitro PD model, Mito improved cell morphology and increased cell viability from 25.06% to 42.44% (p&#xa0;<&#xa0;0.001), while enhancing mitochondrial activity within the cells by a 201% increase in the JC-1 red/green fluorescence ratio (p&#xa0;=&#xa0;0.02). Further analysis suggests that Mito's neuroprotective effects are potentially mediated via integrated modulation of neuroinflammation and ferroptosis pathways. The findings of the in vivo PD model showed that Mito improved motor coordination in the rotational test by 71% (p&#xa0;<&#xa0;0.01) and ameliorated depression-like behavior demonstrating a 13.4% enhancement in Sucrose preference (p&#xa0;<&#xa0;0.001), accompanied by histological evidence of neuroprotection observed in Nissl-stained brain sections and the significant recovery in mitochondrial function by 31.6% (p&#xa0;=&#xa0;0.01). This study is the first to demonstrate that Mito can enter a PD cell model and rescue neuronal and mitochondrial damage in both in vivo and in vitro settings, with transcriptomic analysis revealing the involvement of key molecular pathways related to neuroinflammation and ferroptosis. This offers new insights and prospectus therapeutic strategies for PD as well as a foundation for future research in clinical medicine.