Cilazapril and benazepril mitigate neurodegeneration and α-synuclein accumulation in a cellular model of parkinson’s disease

Parkinson's disease (PD) is characterised by progressive neuronal degeneration and oxidative stress, both of which significantly contribute to its pathology and clinical symptoms. This study investigated the antioxidant, anti-inflammatory and neuroprotective effects of cilazapril and benazepril in an in vitro PD model induced by 6-hydroxydopamine (6-OHDA) in SH-SY5Y neuroblastoma cells. We performed molecular docking of these compounds to dopamine-related receptors (AT1, AT2, D1A, D1B and D2), as well as dynamic simulations. Morphological analysis revealed structural preservation in treated cells, and key biomarkers (MTT, TAS-TOS, IL-10, IL-1β, TNF-α, LDH, MDA, SOD and TGF-β) were evaluated using ELISA. The gene expression of the D1 and D2 receptors was measured using real-time PCR, and the expression of α-synuclein and neuronal nitric oxide synthase was analysed using immunohistochemistry. Both drugs significantly reduced oxidative damage, α-synuclein aggregation and neuroinflammation (*p < 0.05). They modulated genetic pathways involved in dopaminergic signalling and showed high binding affinity for the AT1, AT2, D1A, D1B and D2 receptors. These findings suggest that cilazapril and benazepril exert multi-targeted protective effects that extend beyond simple antioxidant activity, and that they may be effective in treating or mitigating PD-related neurodegeneration.