Neuroprotective Effects of Pregnenolone Against Oxidative Damage in a 6-Hydroxyd opamine-Induced Parkinson’s Disease Cell Model Using SH-SY5Y Cell Line

Abstract

Objective: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons, leading to motor impairments and cognitive deficits. Despite advances in understanding PD’s pathophysiology, effective therapeutic interventions are limited. Oxidative stress, resulting from the overproduction of reactive oxygen and nitrogen species, plays a crucial role in PD progression. Neurosteroids, naturally occurring brain steroids, have been implicated in dopamine signaling regulation and are disrupted in PD. Pregnenolone (Prgn), a neurosteroid, has shown potential neuroprotective properties and antioxidant effects. Methods: In this study, we investigated the neuroprotective potential of Prgn in an in vitro PD model using SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA). Pregnenolone pretreatment significantly improved cell viability and reduced oxidative stress induced by 6-OHDA exposure. Moreover, Prgn treatment led to the modulation of antioxidative biomarkers, restoring cellular redox balance. Results: Our findings suggest that Prgn exerts neuroprotective effects against 6-OHDA-induced neurotoxicity in SH-SY5Y cells by reducing oxidative stress and enhancing cell survival. These results support the exploration of Prgn as a potential therapeutic agent for mitigating PD progression. Conclusion: In conclusion, our study demonstrates that Prgn, a neurosteroid, exhibits promising neuroprotective effects in an in vitro model of PD by attenuating 6-OHDA-induced oxidative damage and preserving the viability and functional integrity of SH-SY5Y cells.

Keywords

• 6-OHDA
• in vitro
• oxidative stress
• Parkinson’s disease
• pregnenolone

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