Work

Dynamic redox monitoring in differentiated human neuroblastoma models of Parkinson’s disease

Year: 2025

Type: article

Abstract: BACKGROUND: Oxidative stress plays a critical role in the degeneration of midbrain dopaminergic (DA) neurons in Parkinson's disease (PD). However, therapies targeting redox mechanisms are hindered by a lack of scalable and inexpensive redox-focused preclinical models. METHODS: We stably expressed the glutathione-specific redox-sensitive fluorescent protein Grx-roGFP2 in SH-SY5Y and BE(2)-M17 neuroblastoma cell lines. We developed an improved differentiation protocol using staurosporine and dbcAMP to enhance dopaminergic-like characteristics, assessed by DA marker expression, and characterized responses to PD-relevant toxins. RESULTS: BE(2)-M17 cells expressed higher DA markers than SH-SY5Y cells, and the improved protocol further increased DA markers. Differentiated neuroblastoma cells with dopaminergic-like features showed greater sensitivity to MPP+ and paraquat, with reduced viability, increased oxidative stress, glutathione oxidation, decreased TH expression, and altered neuronal morphology, paralleling patterns observed in PD-related oxidative injury. roGFP2 enabled robust, real-time redox monitoring, correlating oxidative stress with phenotype. Sublethal toxin exposure caused mitochondrial alterations and redox shifts. Pretreatment with N-acetyl-L-cysteine (NAC) mitigated oxidative stress, improved viability, and partially restored TH expression and morphology. CONCLUSION: This neuroblastoma-based model with dopaminergic-like features enables scalable, real-time redox monitoring and detailed phenotypic analyses. It expands access to redox biology platforms for investigating neurodegeneration and evaluating antioxidant therapeutic strategies relevant to neurodegeneration.

Source: Redox Report

DOI: 10.1080/13510002.2025.2595781