Oxidative stress in neurodegeneration: in vitro models for investigating cellular damage and neuroprotective strategies

Abstract

Neurodegenerative disorders such as Parkinson’s disease (PD) are driven by complex and multifactorial mechanisms, among which oxidative stress plays a central pathogenic role. A sustained imbalance between reactive oxygen species (ROS) production and antioxidant defenses contributes to mitochondrial dysfunction, lipid peroxidation, and dopaminergic neuronal loss. This review focuses on oxidative stress-induced neurodegeneration and explores how in vitro models can be effectively used to study the cellular consequences of oxidative damage. Particular emphasis is placed on toxin-based models, including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP⁺), as well as cellular systems such as immortalized cell lines, primary neurons, and induced pluripotent stem cell (iPSC)-derived neurons. The applicability, advantages, and limitations of each model are discussed in the context of mimicking PD-related oxidative damage and screening for neuroprotective strategies. Ultimately, this review underscores the importance of selecting appropriate in vitro models for dissecting oxidative stress pathways and advancing neuroprotective research in PD.