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Autoimmune processes have been involved in neurodegeneration, including Parkinson\u2019s disease (PD). AT1 autoantibodies (AT1-AA) enhance neurodegeneration and PD, which was related to increased neuronal oxidative stress and neuroinflammation. However, the effect of AT1-AA on \u03b1-synuclein aggregation, a major factor in PD progression, has not been studied. In cultures of dopaminergic neurons, we observed that AT1-AA promote aggregation of \u03b1-synuclein, as AT1-AA upregulated major mechanisms involved in the \u03b1-synuclein aggregation process such as NADPH-oxidase activation and intracellular calcium raising. The results further support the role of AT1 receptors in dopaminergic neuron degeneration, and several recent clinical studies observing the neuroprotective effects of AT1 receptor blockers.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1457459","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T06:11:44Z","timestamp":1731305504000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Angiotensin type-1 receptor autoantibodies promote alpha-synuclein aggregation in dopaminergic neurons"],"prefix":"10.3389","volume":"15","author":[{"given":"Lucia","family":"Lage","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana I.","family":"Rodr\u00edguez-Perez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L.","family":"Labandeira-Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Dominguez-Meijide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2021.114673","article-title":"Angiotensin ii receptor type 1 - an update on structure, expression and pathology","volume":"192","author":"Eckenstaler","year":"2021","journal-title":"Biochem Pharmacol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s40035-024-00410-3","article-title":"The role of the brain renin-angiotensin system in parkinson S disease","volume":"13","author":"Labandeira-Garcia","year":"2024","journal-title":"Transl Neurodegener"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01061-1","article-title":"Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in parkinson\u2019s disease","volume":"25","author":"Kamath","year":"2022","journal-title":"Nat Neurosci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00684-6","article-title":"Inflammation and immune dysfunction in parkinson disease","volume":"22","author":"Tansey","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1038\/s41577-021-00543-w","article-title":"Autoantibodies in neurological disease","volume":"21","author":"Pruss","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.564526","article-title":"What makes antibodies against G protein-coupled receptors so special? 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