Angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson’s disease
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, includ...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2022-01-01
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| Series: | Neural Regeneration Research |
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| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2022;volume=17;issue=5;spage=1138;epage=1145;aulast=Gao |
| _version_ | 1818559292077244416 |
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| author | Qing Gao Rui Chen Liang Wu Qing Huang Xi-Xi Wang You-Yong Tian Ying-Dong Zhang |
| author_facet | Qing Gao Rui Chen Liang Wu Qing Huang Xi-Xi Wang You-Yong Tian Ying-Dong Zhang |
| author_sort | Qing Gao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T00:23:30Z |
| format | Article |
| id | doaj.art-25732ef14aba47e7a9ae45ae14e8f2fb |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-12-14T00:23:30Z |
| publishDate | 2022-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-25732ef14aba47e7a9ae45ae14e8f2fb2022-12-21T23:25:08ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742022-01-011751138114510.4103/1673-5374.324854Angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson’s diseaseQing GaoRui ChenLiang WuQing HuangXi-Xi WangYou-Yong TianYing-Dong ZhangAbnormal 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.http://www.nrronline.org/article.asp?issn=1673-5374;year=2022;volume=17;issue=5;spage=1138;epage=1145;aulast=Gaoα-synuclein; apoptosis; autophagy; dopaminergic neuron; lewy bodies; neurodegenerative diseases; parkinson’s disease; renin-angiotensin system; rotenone; substantia nigra |
| spellingShingle | Qing Gao Rui Chen Liang Wu Qing Huang Xi-Xi Wang You-Yong Tian Ying-Dong Zhang Angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson’s disease Neural Regeneration Research α-synuclein; apoptosis; autophagy; dopaminergic neuron; lewy bodies; neurodegenerative diseases; parkinson’s disease; renin-angiotensin system; rotenone; substantia nigra |
| title | Angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson’s disease |
| title_full | Angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson’s disease |
| title_fullStr | Angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson’s disease |
| title_full_unstemmed | Angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson’s disease |
| title_short | Angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson’s disease |
| title_sort | angiotensin 1 7 reduces α synuclein aggregation by enhancing autophagic activity in parkinson s disease |
| topic | α-synuclein; apoptosis; autophagy; dopaminergic neuron; lewy bodies; neurodegenerative diseases; parkinson’s disease; renin-angiotensin system; rotenone; substantia nigra |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2022;volume=17;issue=5;spage=1138;epage=1145;aulast=Gao |
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