课题基金基金详情
基于应激敏感蛋白RTP801介导的α-Synuclein自噬降解障碍解析人参皂苷Rg1延缓PD病理进程的分子机制
结题报告
批准号:
81973499
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
张钊
学科分类:
中药神经精神药理
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
张钊
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中文摘要
帕金森病(PD)属中医颤证范畴,肝血不足、肾气亏虚为发病之源。情志不舒、肝失疏泄导致的气机失调、筋脉失养是加重PD的关键机制。人参兼具大补元气及安神定志之功效,被历代医家用于颤证治疗疗效确切。人参皂苷Rg1是人参的标志性成分,兼有抗应激与改善PD症状的功效,但其是否可延缓PD进程尚未明确。本项目前期研究发现,RTP801是诱导PD发病的关键因子。长期应激可导致RTP801异常增加,引发α-Synuclein自噬降解障碍,加重PD病理进程。Rg1可抑制应激造成的RTP801水平升高,改善PD症状,表明Rg1具有延缓PD病理进程的潜能。基于此,我们提出Rg1可通过抑制RTP801介导的α-Synuclein自噬降解障碍延缓PD病理进程的科学假说。本项目拟采用基因编辑、自噬流监控、Bi-FC聚集可视化、转录结合位点突变等技术手段,探讨Rg1延缓PD进程的作用效果及机制,提升传统中药的应用价值。
英文摘要
Parkinson's disease (PD) belongs to the category of tremor syndrome according to the traditional Chinese medical science. The key mechanism of aggravation is the imbalance of qi and tendon and vessel malnutrition. Ginseng has the effect of reinforcing vital energy and calming the mind, which has been used by doctors in past dynasties for the treatment of tremor syndrome. Ginsenoside Rg1 is a representative component of ginseng, which can both resist stress and improve PD symptoms, but whether it can delay the pathological process of PD has not been determined. The previous study of this project found that RTP801 was a key factor for the aggravation of PD induced by stress, and long-term stress could lead to an abnormal increase in RTP801, leading to the disorder of α-synuclein autophagic degradation and aggravating the pathological process of PD. Rg1 can significantly inhibit the increase of RTP801 level caused by stress and improve PD symptoms, indicating that Rg1 has the potential to delay the pathological process of PD aggravated by environmental stress. Based on this, we proposed the scientific hypothesis that Rg1 can delay the pathological process of PD through inhibiting the α-synuclein autophagic degradation disorder mediated by RTP801. In this project, gene editing, autophagic flux monitoring, Bi-Fc aggregation visualization, transcription binding site mutation and other experiments are adopted to explore the delayed effect of Rg1 on the pathological process of PD, so as to enhance the application value of traditional Chinese medicine.
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DOI:10.3389/fphar.2021.671734
发表时间:2021
期刊:Frontiers in pharmacology
影响因子:5.6
作者:Peng Y;Chu S;Yang Y;Zhang Z;Pang Z;Chen N
通讯作者:Chen N
Low corticosterone levels attenuate late life depression and enhance glutamatergic neurotransmission in female rats
低皮质酮水平可减轻雌性大鼠晚年抑郁症并增强谷氨酸能神经传递
DOI:10.1038/s41401-020-00536-w
发表时间:2020-10-07
期刊:ACTA PHARMACOLOGICA SINICA
影响因子:8.2
作者:Chu, Shi-feng;Zhang, Zhao;Chen, Nai-hong
通讯作者:Chen, Nai-hong
Rg1 exerts protective effect in CPZ-induced demyelination mouse model via inhibiting CXCL10-mediated glial response
Rg1 通过抑制 CXCL10 介导的神经胶质反应对 CPZ 诱导的脱髓鞘小鼠模型发挥保护作用
DOI:10.1038/s41401-021-00696-3
发表时间:2021-06-08
期刊:ACTA PHARMACOLOGICA SINICA
影响因子:8.2
作者:Dong, Yi-xiao;Chu, Shi-feng;Chen, Nai-hong
通讯作者:Chen, Nai-hong
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