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http://hdl.handle.net/2445/175330
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DC Field | Value | Language |
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dc.contributor.author | Rivas‐Santisteban, Rafael | - |
dc.contributor.author | Rodríguez Pérez, Ana I. | - |
dc.contributor.author | Muñoz, Ana | - |
dc.contributor.author | Reyes Resina, Irene | - |
dc.contributor.author | Labandeira García, José L. | - |
dc.contributor.author | Navarro Brugal, Gemma | - |
dc.contributor.author | Franco Fernández, Rafael | - |
dc.date.accessioned | 2021-03-18T13:11:08Z | - |
dc.date.available | 2021-03-18T13:11:08Z | - |
dc.date.issued | 2020-02-01 | - |
dc.identifier.issn | 1015-8987 | - |
dc.identifier.uri | http://hdl.handle.net/2445/175330 | - |
dc.description.abstract | Background/Aims : The renin-angiotensin system (RAS) is altered in Parkinson's disease (PD), a disease due to substantia nigra neurodegeneration and whose dopamine-replacement therapy, using the precursor levodopa, leads to dyskinesias as the main side effect. Angiotensin AT 1 and AT 2 receptors, mainly known for their role in regulating water homeostasis and blood pressure and able to form heterodimers (AT 1/2 Hets), are present in the central nervous system. We assessed the functionality and expression of AT 1/2 Hets in Parkinson Disease (PD). Methods: Immunocytochemistry was used to analyze the colocalization between angiotensin receptors, bioluminescence resonance energy transfer was used to detect AT 1/2 Hets. Calcium and cAMP determination, MAPK activation and label-free assays were performed to characterize signaling. Proximity ligation assays was used to quantify receptor expression in microglial cells and brain striatal slices. Results: We confirmed that AT 1 and AT 2 receptors form AT 1/2 Hets that are expressed in cells of the central nervous system. AT 1/2 Hets are novel functional units with particular signaling properties. Importantly, the coactivation of the two receptors in the heteromer reduces the signaling output of angiotensin. Remarkably, AT 1/2 Hets that are expressed in both striatal neurons and microglia show a cross-potentiation, i.e. candesartan, the antagonist of AT 1 increases the effect of AT 2 receptor agonists. In addition, the level of expression in the unilateral 6-OH-dopamine lesion rat PD model increases upon disease progression and is maximal in dyskinetic animals. Conclusion: The results indicate that boosting the action of neuroprotective AT 2 receptors using an AT 1 receptor antagonist constitutes a promising therapeutic strategy in PD. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Karger | - |
dc.relation.isformatof | Reproducció del document publicat a: | - |
dc.relation.ispartof | Cellular Physiology and Biochemistry, 2020 | - |
dc.rights | cc-by-nc (c) Karger, 2020 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/3.0/es | - |
dc.source | Articles publicats en revistes (Bioquímica i Fisiologia) | - |
dc.subject.classification | Receptors cel·lulars | - |
dc.subject.classification | Malaltia de Parkinson | - |
dc.subject.classification | Malalties neurodegeneratives | - |
dc.subject.other | Cell receptors | - |
dc.subject.other | Parkinson's disease | - |
dc.subject.other | Neurodegenerative Diseases | - |
dc.title | Angiotensin AT1 and AT2 receptors heteromer expression in microglia correlates with Parkinson's disease progression in the hemilesioned rat model of the disease | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 699979 | - |
dc.date.updated | 2021-03-18T13:11:08Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Articles publicats en revistes (Bioquímica i Fisiologia) |
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