Neuroprotective activities of sertraline, tiagabine, and bicifadine with autophagy-inducing potentials in a 6-hydroxidopamine-treated Parkinson’s disease cell model

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Abstract Parkinson’s disease (PD) is a prevalent neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra. The development of effective neuroprotective therapies is crucial for mitigating the devastating effects of PD, and autophagy induction has recently emerged as a promising neuroprotective strategy. This study aimed to identify autophagy-inducing compounds and evaluate their neuroprotective activity in the chemical library. Among 3,200 chemicals consisting of FDA-approved drugs or are being evaluated in clinical trials, 547 chemicals indicating CNS diseases were filtered in, and 3 compounds (sertraline, tiagabine and bicifadine) were finally identified to exhibit the autophagy-inducing activity and the neuroprotective activity in 6-hydroxydopamine (6-OHDA)-induced PC12 neuronal damaged PD model. Furthermore, Neurochemical profiling also revealed that 3 chemicals alleviated 6-OHDA-induced neurochemical pathway disruptions in PC12 cells. In conclusion, sertraline, tiagabine, and bicifadine, not only exhibited autophagy-inducing potential but also demonstrated significant neuroprotective activity with the change of neurochemical profiles against 6-OHDA-induced neurotoxicity in PD model, suggesting that 3 autophagy-inducing chemicals could be repositioned for PD to protect the neuronal cells.

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