Abstract：
Mitochondrial dysfunction is the main pathological mechanism responsible for the death of midbrain dopaminergic (mDA) neurons. Thus, mitochondria-targeting therapy is a potential therapeutic strategy for Parkinson\'s disease (PD). Homeodomain transcription factors such as Otx2 can translocate between cells and exert non-cellular autonomous functions in recipient cells to stimulate neuronal survival. In this study, we investigated if exogenous Otx2 acts as a survival factor for mDA neurons by protecting them against MPP+-induced neurotoxicity in vitro. We show that subacute MPTP dosing regimen induces significant reduction in the levels of Otx2 homeoprotein in the ventral midbrain of PD mice. We also show that exogenous Otx2-myc recombinant protein protected primary mDA neurons against MPP+ by interacting with ATP5a1and promoting ATP synthesis.
摘要：
线粒体功能障碍是导致中脑多巴胺能（mDA）神经元死亡的主要病理机制。因此，线粒体靶向治疗是帕金森病（PD）的潜在治疗策略。同源结构域转录因子如Otx2可以在细胞之间易位并在受体细胞中发挥非细胞自主功能以刺激神经元存活。在这项研究中,我们研究了外源性Otx2是否通过在体外保护mDA神经元免受MPP诱导的神经毒性而充当mDA神经元的存活因子。我们表明，亚急性MPTP给药方案诱导PD小鼠腹侧中脑Otx2同源异型蛋白水平显着降低。我们还表明，外源Otx2-myc重组蛋白通过与ATP5a1相互作用并促进ATP合成来保护原代mDA神经元免受MPP的侵害。
