| Autor: |
Sanz FJ; Departamento de Genética, Facultad de Ciencias Biológicas, Universidad de Valencia, Burjassot 46100, Spain.; Instituto Universitario de Biotecnología y Biomedicina (BIOTECMED), Universidad de Valencia, Burjassot 46100, Spain., Solana-Manrique C; Departamento de Genética, Facultad de Ciencias Biológicas, Universidad de Valencia, Burjassot 46100, Spain.; Instituto Universitario de Biotecnología y Biomedicina (BIOTECMED), Universidad de Valencia, Burjassot 46100, Spain.; Departamento de Fisioterapia, Facultad de Ciencias de La Salud, Universidad Europea de Valencia, Valencia 46010, Spain., Paricio N; Departamento de Genética, Facultad de Ciencias Biológicas, Universidad de Valencia, Burjassot 46100, Spain.; Instituto Universitario de Biotecnología y Biomedicina (BIOTECMED), Universidad de Valencia, Burjassot 46100, Spain. |
| Abstrakt: |
Parkinson's 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 for new and more effective therapies, our group carried out a high-throughput screening assay, identifying several candidate compounds that are able to improve locomotor ability in DJ-1β mutant flies (a Drosophila model of familial PD) and 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, our results show that VIN might be exerting its beneficial role, at least partially, by the inhibition of voltage-gated sodium channels. Therefore, we propose that these channels might be a promising target in the search for new compounds to treat PD and that VIN represents a potential therapeutic treatment for the disease. |
