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oai:figshare.com:article/33965878 2026-09-22T15:02:11Z category_696 portal_316 item_type_3 month_year_09_2026

Table 1_Angiotensin II-induced hypertension does not exacerbate α-SYNUCLEIN pathology in a mouse model of Parkinson’s disease.docx Ignacio Silva-Llanes (20621009) Daniel Flores-Téllez (17125236) Wilfrido J. Arrua (25090654) Naoual B. El Jouhar (25090657) Eduardo Oliver (5879252) Ana Martínez (218665) Ana M. Briones (7951520) Isabel Lastres-Becker (246295) Genetic Immunology α-SYNUCLEIN angiotensin-II gasdermin hypertension neurodegeneration neuroinflammation Parkinson’s disease <p>Parkinson’s disease (PD) is characterized by progressive degeneration of nigrostriatal dopaminergic neurons accompanied by chronic neuroinflammation and α-SYNUCLEIN (α-SYN) aggregation. Increasing evidence suggests that cardiovascular comorbidities, including arterial hypertension, may contribute to neurodegenerative processes through vascular dysfunction and sustained inflammatory signaling. However, whether hypertension directly exacerbates α-SYN-induced neurodegeneration and inflammasome activation remains unclear. Here, we investigated the impact of chronic Angiotensin II (AngII)-induced hypertension in an adeno-associated viral vector (AAV)-based mouse model of PD driven by unilateral overexpression of human α-SYN in the Substantia Nigra (SN). Chronic AngII infusion produced a robust hypertensive phenotype but did not aggravate α-SYN-induced loss of tyrosine hydroxylase-positive dopaminergic neurons. Similarly, hypertension failed to modify α-SYN-driven astrogliosis, microgliosis, or microglial morphological activation. Molecular analyses revealed that α-SYN overexpression markedly increased the expression of inflammatory mediators and pyroptosis-related genes, including Nlrp3, Asc, Casp1, Il1b, Il18rap, and Gsdmd. Nevertheless, hypertension did not potentiate these responses. Immunofluorescence analyses further demonstrated that GSDMD expression was predominantly localized in IBA1-positive microglial cells and was significantly elevated following α-SYN overexpression independently of hypertensive status. Collectively, these findings indicate that chronic AngII-induced hypertension is insufficient to exacerbate early α-SYN-mediated neurodegeneration, gliosis, or inflammasome-associated pyroptotic pathways in the SN. Our study suggests that α-SYN pathology itself constitutes the dominant driver of neuroinflammatory activation in this experimental paradigm and that additional vascular or aging-related mechanisms may be required for hypertension to significantly influence PD progression.</p> 2026-09-22T15:02:11Z Dataset Dataset 10.3389/fimmu.2026.1894579.s002 https://figshare.com/articles/dataset/Table_1_Angiotensin_II-induced_hypertension_does_not_exacerbate_-SYNUCLEIN_pathology_in_a_mouse_model_of_Parkinson_s_disease_docx/33965878 CC BY 4.0