Disease-modifying effects of Vincamine supplementation inDrosophilaand human cell models of Parkinson’s disease

Abstract

Parkinson's disease (PD) is an incurable neurodegenerative disorder caused by the selective loss of dopaminergic neurons in thesubstantia 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 inDJ-1βmutant flies (aDrosophilamodel of familial PD) and to reduce oxidative stress (OS)-induced lethality inDJ-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 bothDrosophilaand 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 inDJ-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.

A review on the nutraceuticals of Parkinson's disease

“…These contain anti-inflammatory properties and could help reduce inflammation in the brain that is involved in PD. Studies have shown that taking omega-3 supplements may help with the motor symptoms of PD [52]. Treatment with docosahexaenoic acid enhanced antioxidant defence, reduced the death of dopaminergic neurons, and increased motor performance in mice challenged with MPTP.…”

“…As a primary polyphenol in green tea, epigallocatechin-3gallate (EGCG) is known to be beneficial for those who have PD since it is well known for its properties of being antiinflammatory, antioxidant and neuroprotective. According to an in vitro study, EGCG and its metabolites can pass through the blood-brain barrier and cause neuritogenesis in the brain parenchyma [52]. The preventive effect of EGCG against dangerous DA metabolites is contributed by its catechol-like structure.…”

“…In mice with PD caused by rotenone, ginsenoside Rg3 also enhanced motor performance. The neuroprotective benefits of ginsenoside Rg3 are at least partially attributed to its anti-oxidative properties by controlling the regulatory subunit of glutathione cysteine ligase and modulatory subunit expression [52].…”

“…Significant antinociceptive, neuroprotective and neurodegenerative properties are exhibited by rosmarinic acid [64]. It was proven that rosmarinic acid upregulated HO-1 and inhibited the expression of -synuclein to provide defence against ironinduced -synuclein aggregation [52].…”

“…It also prevents the aggregation of -synuclein in mice suffering from PD. This action is largely mediated by activating the Akt1/SIR signalling pathway [52].…”