帕金森病（PD）是神经系统退行性疾病，其发病缓慢、隐匿且进行性加重。早期主要是非运动症状，如嗅觉功能减退等，晚期出现运动障碍，严重影响生存质量。目前尚无早期干预药物，因此研究并开发PD早期干预药物阻止病情进展迫在眉睫。本课题组前期工作将植物药荜茇提纯制备了生物碱单体PLG（多项国家发明专利）具有自主知识产权。并前期研究发现PLG可治疗多种PD模型导致的运动障碍。但PLG是否可以早期干预PD尚不清楚。本课题将利用α-突触核蛋白(α-syn)转基因PD动物模型的早期嗅觉障碍，进行PLG早期PD干预研究并探讨其机制。研究①PLG对α-syn过表达导致的PD早期嗅觉功能减退的干预作用；②PLG对促进嗅神经元再生及发育的作用；③PLG通过线粒体Bcl-2调节自噬、凋亡再平衡的作用影响嗅觉神经元再生；④筛选PLG早期干预PD模型的新靶分子。最终为PD早期干预、阻止或延缓病情进展开发新的药物提供依据。

Parkinson disease (PD) is a neurodegenerative disorder and the development is slowly and progressing. Olfactory dysfunction, the most typical non-motor symptom, can precede motor deficits by 10–20 years, seriously affects the patients’ quality of life. There is no effective drug in the early stages of PD. Therefore, exploring and developing novel medicine is extremely urgent. Our previous study showed that Piper longum L. alkaloids PLG prevent form motor deficits in various PD models; however, whether PLG can early intervene to PD pathogenesis is still unknown. This study investigated the protective effects of PLG in α-synuclein (α-syn) induced PD model, aim to: ①whether PLG can prevent from olfactory deficits in α-syn transgenic mice, and further delay or block the progression of this disease; ②whether PLG can improve olfactory sensory neurons regeneration and development; ③ whether PLG can restore the balance of autophagy and apoptosis by targeting Bcl-2; ④ exploring novel intervention target of PLG. Our study provides a clue for the pharmaceutical development of PD.