Table 1_Angiotensin II-induced hypertension does not exacerbate α-SYNUCLEIN pathology in a mouse model of Parkinson’s disease.docx

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>