Growing evidence suggests that oxidative stress plays a critical role in neuronal destruction characteristic of Parkinson's disease (PD). However, the molecular mechanisms of oxidative stress-mediated dopaminergic cell death are far from clear. In the current investigation, we tested the hypothesis that acrolein, an oxidative stress and lipid peroxidation (LPO) product, is a key factor in the pathogenesis of PD. Using a combination of in vitro, in vivo, and cell free models, coupled with anatomical, functional, and behavioral examination, we found that acrolein was elevated in 6-OHDA-injected rats, and behavioral deficits associated with 6-OHDA could be mitigated by the application of the acrolein scavenger hydralazine, and mimicked by injection of acrolein in healthy rats. Furthermore, hydralazine alleviated neuronal cell death elicited by 6-OHDA and another PD-related toxin, rotenone, in vitro. We also show that acrolein can promote the aggregation of alpha-synuclein, suggesting that alpha-synuclein self-assembly, a key pathological phenomenon in human PD, could play a role in neurotoxic effects of acrolein in PD models. These studies suggest that acrolein is involved in the pathogenesis of PD, and the administration of anti-acrolein scavengers such as hydralazine could represent a novel strategy to alleviate tissue damage and motor deficits associated with this disease.

越来越多的证据表明，氧化应激在帕金森氏病（PD）的神经元破坏特征中起着至关重要的作用。然而，氧化应激介导的多巴胺能细胞死亡的分子机制尚不清楚。在当前的研究中，我们测试了以下假设：氧化应激和脂质过氧化（LPO）产物丙烯醛是PD发病机理的关键因素。结合使用体外，体内，无细胞模型以及解剖，功能和行为检查，我们发现注射6-OHDA的大鼠中丙烯醛升高，并且可以通过应用丙烯醛清除剂肼苯哒嗪来减轻与6-OHDA相关的行为缺陷，并通过在健康大鼠中注射丙烯醛来模拟。此外，肼屈嗪在体外减轻了6-OHDA和另一种PD相关毒素鱼藤酮引起的神经元细胞死亡。。我们还表明，丙烯醛可以促进α-突触核蛋白的聚集，表明α-突触核蛋白的自组装是人类PD中的关键病理现象，可能在PD模型中的丙烯醛的神经毒性作用中起作用。这些研究表明，丙烯醛与PD的发病机理有关，抗丙烯醛清除剂如肼屈嗪的给药可能代表减轻与该疾病相关的组织损伤和运动功能障碍的一种新策略。