Angiotensin-(1-7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson's disease.
Angiotensin-(1-7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson's disease.
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DOI：
10.4103/1673-5374.324854
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发表时间：
2022-05
影响因子：
6.1
通讯作者：
Zhang YD
中科院分区：
文献类型：
--
作者：
Gao Q;Chen R;Wu L;Huang Q;Wang XX;Tian YY;Zhang YD
α-突触核蛋白的异常积累有助于黑质中路易体的形成，这被认为是帕金森病的典型病理标志。最近的研究表明，血管紧张素-（1-7）在包括帕金森病在内的几种神经退行性疾病中起着至关重要的作用，但其潜在的机制仍然是难以捉摸的。本研究以雄性SD大鼠腹腔注射鱼藤酮4周建立帕金森病模型。我们研究了血管紧张素-（1-7）是否是神经保护在这个模型中，连续给予血管紧张素-（1-7）到右侧黑质4周。我们发现，血管紧张素-（1-7）输注缓解了特征性帕金森病行为，并减少了黑质中α-突触核蛋白的聚集。从新生Sprague-Dawley大鼠黑质中提取原代多巴胺能神经元，并用鱼藤酮、血管紧张素-（1-7）和/或Mas受体阻断剂A-779处理24小时。在与Mas受体结合后，血管紧张素-（1-7）减弱鱼藤酮处理的细胞中的凋亡和α-突触核蛋白聚集。原代多巴胺能神经元也用血管紧张素-（1-7）和/或自噬抑制剂3-甲基腺嘌呤处理24小时。血管紧张素-（1-7）增加α-突触核蛋白的清除，并增加鱼藤酮处理的细胞的自噬。我们的结论是，血管紧张素-（1-7）减少α-突触核蛋白的聚集，减轻帕金森病的自噬功能障碍。因此，血管紧张素-（1-7）/Mas受体轴在帕金森病的发病机制中起重要作用，血管紧张素-（1-7）对帕金森病具有潜在的治疗价值。所有实验均于2020年1月获得南京市第一医院生物研究伦理委员会批准（批准号：DWSY-2000932）。
Abnormal accumulation of α-synuclein contributes to the formation of Lewy bodies in the substantia nigra, which is considered the typical pathological hallmark of Parkinson's disease. Recent research indicates that angiotensin-(1–7) plays a crucial role in several neurodegenerative disorders, including Parkinson's disease, but the underlying mechanisms remain elusive. In this study, we used intraperitoneal administration of rotenone to male Sprague-Dawley rats for 4 weeks to establish a Parkinson's disease model. We investigated whether angiotensin-(1–7) is neuroprotective in this model by continuous administration of angiotensin-(1–7) into the right substantia nigra for 4 weeks. We found that angiotensin-(1–7) infusion relieved characteristic parkinsonian behaviors and reduced α-synuclein aggregation in the substantia nigra. Primary dopaminergic neurons were extracted from newborn Sprague-Dawley rat substantia nigras and treated with rotenone, angiotensin-(1–7), and/or the Mas receptor blocker A-779 for 24 hours. After binding to the Mas receptor, angiotensin-(1–7) attenuated apoptosis and α-synuclein aggregation in rotenone-treated cells. Primary dopaminergic neurons were also treated with angiotensin-(1–7) and/or the autophagy inhibitor 3-methyladenine for 24 hours. Angiotensin-(1–7) increased α-synuclein removal and increased the autophagy of rotenone-treated cells. We conclude that angiotensin-(1–7) reduces α-synuclein aggregation by alleviating autophagy dysfunction in Parkinson's disease. Therefore, the angiotensin-(1–7)/Mas receptor axis plays an important role in the pathogenesis of Parkinson's disease and angiotensin-(1–7) has potential therapeutic value for Parkinson's disease. All experiments were approved by the Biological Research Ethics Committee of Nanjing First Hospital (approval No. DWSY-2000932) in January 2020.
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影响因子：
4.3
作者：
Javed H;Azimullah S;Haque ME;Ojha SK
通讯作者：
Ojha SK
DOI：
10.1186/s13195-016-0217-7
发表时间：
2016-11-25
期刊：
Alzheimer's research & therapy
影响因子：
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作者：
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通讯作者：
Miners JS
影响因子：
16.6
作者：
Choi, Insup;Zhang, Yuanxi;Yue, Zhenyu
通讯作者：
Yue, Zhenyu
影响因子：
7.1
作者：
Jan A;Jansonius B;Delaidelli A;Bhanshali F;An YA;Ferreira N;Smits LM;Negri GL;Schwamborn JC;Jensen PH;Mackenzie IR;Taubert S;Sorensen PH
通讯作者：
Sorensen PH
血管紧张素 (1-7) 通过改善烟酰胺腺嘌呤二核苷酸磷酸还原氧化酶 4 依赖性活性氧引起的自噬受损来减轻吸烟相关的肺纤维化
DOI：
10.1165/rcmb.2017-0284oc
发表时间：
2018-09-01
影响因子：
6.4
作者：
Pan, Miaoxia;Zheng, Zemao;Meng, Ying
通讯作者：
Meng, Ying