Using a Caenorhabditis elegans Parkinson's Disease Model to Assess Disease Progression and Therapy Efficiency.

Despite Parkinson's Disease (PD) being the second most common neurodegenerative disease, treatment options are limited. Consequently, there is an urgent need to identify and screen new therapeutic compounds that slow or reverse the pathology of PD. Unfortunately, few new therapeutics are being produced, partly due to the low throughput and/or poor predictability of the currently used model organisms and in vivo screening methods. Our objective was to develop a simple and affordable platform for drug screening utilizing the nematode Caenorhabditis elegans. The effect of Levodopa, the "Gold standard" of PD treatment, was explored in nematodes expressing the disease-causing α-synuclein protein. We focused on two key hallmarks of PD: plaque formation and mobility. Exposure to Levodopa ameliorated the mobility defect in C. elegans, similar to people living with PD who take the drug. Further, long-term Levodopa exposure was not detrimental to lifespan. This C. elegans-based method was used to screen a selection of small-molecule drugs for an impact on α-synuclein aggregation and mobility, identifying several promising compounds worthy of further investigation, most notably Ambroxol. The simple methodology means it can be adopted in many labs to pre-screen candidate compounds for a positive impact on disease progression.

An extract of Rosaceae, Solanaceae and Zingiberaceae increases health span and mobility in Caenorhabditis elegans.

BACKGROUND: Members of the Rosaceae, Solanaceae and Zingiberaceae families which include fruits such as cherries, tomatoes and ginger are known to have health promoting effects. There is growing interest in consuming these "functional foods" as a means to increase health and healthy ageing. However, many studies explore the effect of these foods in isolation, not as a blend of multiple functional foods. METHODS: In this study, an extract containing the dried berries, fruits, and roots of members of these families was prepared, which we called Bioact®180. The nematode Caenorhabditis elegans was used to evaluate the effects of Bioact®180 on lifespan and health endpoints, including muscle and mitochondria structure and locomotion. RESULTS: Exposure to the 1000 µg/mL of Bioact®180 extract, containing 4% total phenols, were healthier, as observed by an increase in mean lifespan with and small but significant increase in maximal lifespan. Nematodes exposed to Bioact®180 displayed better mobility in mid-life stages as well as enhanced mitochondrial morphology, which was more comparable to younger animals, suggesting that these worms are protected to some degree from sarcopenia. CONCLUSIONS: Together, our findings reveal that Bioact®180, a blend of fruits and roots from Rosaceae, Solanaceae and Zingiberaceae family members has anti-aging effects. Bioact®180 promotes health and lifespan extension in C. elegans, corresponding to functional improvements in mobility.