Chen Leilei, Huang Yujv, Yu Xing, Lu Jiahong, Jia Wenting, Song Juxian, Liu Liangfeng, Wang Youcui, Huang Yingyu, Xie Junxia, Li Min
Institute of Brain Science and Disease, Qingdao University, Qingdao, China.
Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao University, Qingdao, China.
Front Pharmacol. 2021 Apr 13;12:642900. doi: 10.3389/fphar.2021.642900. eCollection 2021.
Recent studies have shown that impairment of autophagy is related to the pathogenesis of Parkinson's disease (PD), and small molecular autophagy enhancers are suggested to be potential drug candidates against PD. Previous studies identified corynoxine (Cory), an oxindole alkaloid isolated from the Chinese herbal medicine (Miq.) Jacks, as a new autophagy enhancer that promoted the degradation of α-synuclein in a PD cell model. In this study, two different rotenone-induced animal models of PD, one involving the systemic administration of rotenone at a low dosage in mice and the other involving the infusion of rotenone stereotaxically into the pars compacta (SNpc) of rats, were employed to evaluate the neuroprotective effects of Cory. Cory was shown to exhibit neuroprotective effects in the two rotenone-induced models of PD by improving motor dysfunction, preventing tyrosine hydroxylase (TH)-positive neuronal loss, decreasing α-synuclein aggregates through the mechanistic target of the rapamycin (mTOR) pathway, and diminishing neuroinflammation. These results provide preclinical experimental evidence supporting the development of Cory into a potential delivery system for the treatment of PD.
最近的研究表明，自噬功能障碍与帕金森病（PD）的发病机制有关，小分子自噬增强剂被认为是治疗PD的潜在候选药物。先前的研究确定，从中药钩藤（Uncaria rhynchophylla (Miq.) Jacks）中分离出的一种氧化吲哚生物碱——钩藤碱（Cory），是一种新型自噬增强剂，在PD细胞模型中可促进α-突触核蛋白的降解。在本研究中，采用两种不同的鱼藤酮诱导的PD动物模型，一种是给小鼠低剂量全身注射鱼藤酮，另一种是将鱼藤酮立体定向注射到大鼠黑质致密部（SNpc），以评估钩藤碱的神经保护作用。结果显示，钩藤碱在这两种鱼藤酮诱导的PD模型中均表现出神经保护作用，可改善运动功能障碍，防止酪氨酸羟化酶（TH）阳性神经元丢失，通过雷帕霉素机制性靶点（mTOR）通路减少α-突触核蛋白聚集，并减轻神经炎症。这些结果提供了临床前实验证据，支持将钩藤碱开发成治疗PD的潜在给药系统。
