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...
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Wolters Kluwer Medknow Publications
2022-01-01
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doaj-25732ef14aba47e7a9ae45ae14e8f2fb2021-10-07T05:44:39ZengWolters 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 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qing Gao Rui Chen Liang Wu Qing Huang Xi-Xi Wang You-Yong Tian Ying-Dong Zhang |
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 |
author_facet |
Qing Gao Rui Chen Liang Wu Qing Huang Xi-Xi Wang You-Yong Tian Ying-Dong Zhang |
author_sort |
Qing Gao |
title |
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_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_sort |
angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in parkinson’s disease |
publisher |
Wolters Kluwer Medknow Publications |
series |
Neural Regeneration Research |
issn |
1673-5374 |
publishDate |
2022-01-01 |
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. |
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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