Angiotensin type-1 receptor and ACE2 autoantibodies in Parkinson´s disease
Abstract The role of autoimmunity in neurodegeneration has been increasingly suggested. The renin-angiotensin system (RAS) autoantibodies play a major role in several peripheral inflammatory processes. Dysregulation of brain RAS has been involved in neuroinflammation and neurodegeneration. We aimed...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-06-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-022-00340-9 |
| _version_ | 1797641996472418304 |
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| author | Carmen M. Labandeira Maria A. Pedrosa Aloia Quijano Rita Valenzuela Pablo Garrido-Gil Mariña Sanchez-Andrade Juan A. Suarez-Quintanilla Ana I. Rodriguez-Perez Jose L. Labandeira-Garcia |
| author_facet | Carmen M. Labandeira Maria A. Pedrosa Aloia Quijano Rita Valenzuela Pablo Garrido-Gil Mariña Sanchez-Andrade Juan A. Suarez-Quintanilla Ana I. Rodriguez-Perez Jose L. Labandeira-Garcia |
| author_sort | Carmen M. Labandeira |
| collection | DOAJ |
| description | Abstract The role of autoimmunity in neurodegeneration has been increasingly suggested. The renin-angiotensin system (RAS) autoantibodies play a major role in several peripheral inflammatory processes. Dysregulation of brain RAS has been involved in neuroinflammation and neurodegeneration. We aimed to know whether angiotensin type-1 receptor (AT1) autoantibodies (AT1 agonists) and angiotensin-converting enzyme 2 (ACE2) autoantibodies (ACE2 antagonists) may be involved in Parkinson’s disease (PD) progression and constitute a new therapeutical target. Both AT1 and ACE2 serum autoantibodies were higher in a group of 117 PD patients than in a group of 106 controls. Serum AT1 autoantibodies correlated with several cytokines, particularly Tumor Necrosis Factor Ligand Superfamily Member 14 (TNFSF14, LIGHT), and 27-hydroxycholesterol levels. Serum ACE2 autoantibodies correlated with AT1 autoantibodies. Both autoantibodies were found in cerebrospinal fluid (CSF) of four PD patients with CSF samples. Consistent with the observations in patients, experimental dopaminergic degeneration, induced by 6-hydroxydopamine, increased levels of autoantibodies in serum and CSF in rats, as well as LIGHT levels and transglutaminase activity in rat substantia nigra. In cultures, administration of AT1 autoantibodies enhanced dopaminergic neuron degeneration and increased levels of neuroinflammation markers, which was inhibited by the AT1 antagonist candesartan. The results suggest dysregulation of RAS autoantibodies as a new mechanism that can contribute to PD progression. Therapeutical strategies blocking the production, or the effects of these autoantibodies may be useful for PD treatment, and the results further support repurposing AT1 blockers (ARBs) as treatment against PD progression. |
| first_indexed | 2024-03-11T13:53:48Z |
| format | Article |
| id | doaj.art-f83718c455114c328bfe7464be77c6e6 |
| institution | Directory Open Access Journal |
| issn | 2373-8057 |
| language | English |
| last_indexed | 2024-03-11T13:53:48Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj.art-f83718c455114c328bfe7464be77c6e62023-11-02T07:56:15ZengNature Portfolionpj Parkinson's Disease2373-80572022-06-018111210.1038/s41531-022-00340-9Angiotensin type-1 receptor and ACE2 autoantibodies in Parkinson´s diseaseCarmen M. Labandeira0Maria A. Pedrosa1Aloia Quijano2Rita Valenzuela3Pablo Garrido-Gil4Mariña Sanchez-Andrade5Juan A. Suarez-Quintanilla6Ana I. Rodriguez-Perez7Jose L. Labandeira-Garcia8Research Center for Molecular Medicine and Chronic diseases (CIMUS), IDIS, University of Santiago de CompostelaResearch Center for Molecular Medicine and Chronic diseases (CIMUS), IDIS, University of Santiago de CompostelaResearch Center for Molecular Medicine and Chronic diseases (CIMUS), IDIS, University of Santiago de CompostelaResearch Center for Molecular Medicine and Chronic diseases (CIMUS), IDIS, University of Santiago de CompostelaResearch Center for Molecular Medicine and Chronic diseases (CIMUS), IDIS, University of Santiago de CompostelaObstetric Service, University Clinical Hospital of Santiago de CompostelaPrimary Health-Care Unit Fontiñas, IDISResearch Center for Molecular Medicine and Chronic diseases (CIMUS), IDIS, University of Santiago de CompostelaResearch Center for Molecular Medicine and Chronic diseases (CIMUS), IDIS, University of Santiago de CompostelaAbstract The role of autoimmunity in neurodegeneration has been increasingly suggested. The renin-angiotensin system (RAS) autoantibodies play a major role in several peripheral inflammatory processes. Dysregulation of brain RAS has been involved in neuroinflammation and neurodegeneration. We aimed to know whether angiotensin type-1 receptor (AT1) autoantibodies (AT1 agonists) and angiotensin-converting enzyme 2 (ACE2) autoantibodies (ACE2 antagonists) may be involved in Parkinson’s disease (PD) progression and constitute a new therapeutical target. Both AT1 and ACE2 serum autoantibodies were higher in a group of 117 PD patients than in a group of 106 controls. Serum AT1 autoantibodies correlated with several cytokines, particularly Tumor Necrosis Factor Ligand Superfamily Member 14 (TNFSF14, LIGHT), and 27-hydroxycholesterol levels. Serum ACE2 autoantibodies correlated with AT1 autoantibodies. Both autoantibodies were found in cerebrospinal fluid (CSF) of four PD patients with CSF samples. Consistent with the observations in patients, experimental dopaminergic degeneration, induced by 6-hydroxydopamine, increased levels of autoantibodies in serum and CSF in rats, as well as LIGHT levels and transglutaminase activity in rat substantia nigra. In cultures, administration of AT1 autoantibodies enhanced dopaminergic neuron degeneration and increased levels of neuroinflammation markers, which was inhibited by the AT1 antagonist candesartan. The results suggest dysregulation of RAS autoantibodies as a new mechanism that can contribute to PD progression. Therapeutical strategies blocking the production, or the effects of these autoantibodies may be useful for PD treatment, and the results further support repurposing AT1 blockers (ARBs) as treatment against PD progression.https://doi.org/10.1038/s41531-022-00340-9 |
| spellingShingle | Carmen M. Labandeira Maria A. Pedrosa Aloia Quijano Rita Valenzuela Pablo Garrido-Gil Mariña Sanchez-Andrade Juan A. Suarez-Quintanilla Ana I. Rodriguez-Perez Jose L. Labandeira-Garcia Angiotensin type-1 receptor and ACE2 autoantibodies in Parkinson´s disease npj Parkinson's Disease |
| title | Angiotensin type-1 receptor and ACE2 autoantibodies in Parkinson´s disease |
| title_full | Angiotensin type-1 receptor and ACE2 autoantibodies in Parkinson´s disease |
| title_fullStr | Angiotensin type-1 receptor and ACE2 autoantibodies in Parkinson´s disease |
| title_full_unstemmed | Angiotensin type-1 receptor and ACE2 autoantibodies in Parkinson´s disease |
| title_short | Angiotensin type-1 receptor and ACE2 autoantibodies in Parkinson´s disease |
| title_sort | angiotensin type 1 receptor and ace2 autoantibodies in parkinson´s disease |
| url | https://doi.org/10.1038/s41531-022-00340-9 |
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