Pedrosa Sánchez, María ÁngelesLabandeira Guerra, Carmen MaríaValenzuela Limiñana, RitaQuijano Ocampo, AloiaSánchez Andrade, MariñaSuárez Quintanilla, JuanLanciego Pérez, José LuisLabandeira García, José LuisRodríguez Pérez, Ana Isabel2023-01-172023-01-172022Brain, Behavior, and Immunity 108 (2023). https://doi.org/10.1016/j.bbi.2022.12.009http://hdl.handle.net/10347/29904The metabolic syndrome has been associated to chronic peripheral inflammation and related with neuroinflammation and neurodegeneration, including Parkinson’s disease. However, the responsible mechanisms are unclear. Previous studies have involved the brain renin-angiotensin system in progression of Parkinson’s disease and the angiotensin receptor type 1 (AT1) has been recently revealed as a major marker of dopaminergic vulnerability in humans. Dysregulation of tissue renin-angiotensin system is a key common mechanism for all major components of metabolic syndrome. Circulating AT1 agonistic autoantibodies have been observed in several inflammation-related peripheral processes, and activation of AT1 receptors of endothelial cells, dopaminergic neurons and glial cells have been observed to disrupt endothelial blood -brain barrier and induce neurodegeneration, respectively. Using a rat model, we observed that metabolic syndrome induces overactivity of nigral pro-inflammatory renin-angiotensin system axis, leading to increase in oxidative stress and neuroinflammation and enhancing dopaminergic neurodegeneration, which was inhibited by treatment with AT1 receptor blockers (ARBs)eng© 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by- nc/4.0/)Atribución-NoComercial 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc/4.0/AutoimmunityACE2Blood–brain-barrierDiabetes27-HydroxycholesterolHypertensionObesityNeurodegenerationParkinsonRenin-angiotensin systemjournal article10.1016/j.bbi.2022.12.0090889-1591open access