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bioRxiv · 10.1101/2022.12.28.522104

Disease-modifying effects of Vincamine supplementation in Drosophila and human cell models of Parkinson's disease

Sanz, F. J.·Solana-Manrique, C.·Paricio, N.
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Abstract

Parkinsons disease (PD) is an incurable neurodegenerative disorder caused by the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Current therapies are only symptomatic, and are not able to stop or delay its progression. In order to search new and more effective therapies, our group carried out a high-throughput screening assay, identifying several candidate compounds able to suppress motor defects in DJ-1{beta} mutant flies (a Drosophila model of familial PD) and to reduce oxidative stress (OS)-induced lethality in DJ-1-deficient SH-SY5Y human cells. One of them was vincamine (VIN), a natural alkaloid obtained from the leaves of Vinca minor. Our results showed that VIN is able to suppress PD-related phenotypes in both Drosophila and human cell PD models. Specifically, VIN reduced OS levels in PD model flies. Besides, VIN diminished OS-induced lethality by decreasing apoptosis, increased mitochondrial viability and reduced OS levels in DJ-1-deficient human cells. In addition, we have demonstrated that VIN is able to exert its beneficial role, at least partially, by the inhibition of voltage-gated Na+ channels. Therefore, we propose that these channels might be a promising target in the search for new compounds to treat PD, and that VIN constitutes a potential therapeutic treatment for the disease.

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Sanz, F. J., Solana-Manrique, C., Paricio, N.. 2022-12-29. Disease-modifying effects of Vincamine supplementation in Drosophila and human cell models of Parkinson's disease. https://doi.org/10.1101/2022.12.28.522104

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