Hughes Samantha, van Dop Maritza, Kolsters Nikki, van de Klashorst David, Pogosova Anastasia, Rijs Anouk M
HAN BioCentre, HAN University of Applied Sciences, Laan van Scheut 2, 6525 EM Nijmegen, The Netherlands.
A-LIFE Amsterdam Institute for Life and Environment, Section Environmental Health and Toxicology, Vrije Univeristeit Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.
Pharmaceuticals (Basel). 2022 Apr 22;15(5):512. doi: 10.3390/ph15050512.
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 . 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 , similar to people living with PD who take the drug. Further, long-term Levodopa exposure was not detrimental to lifespan. This -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.
尽管帕金森病（PD）是第二常见的神经退行性疾病，但治疗选择有限。因此，迫切需要识别和筛选能够减缓或逆转PD病理的新治疗化合物。不幸的是，新疗法的研发进展缓慢，部分原因是目前使用的模式生物和体内筛选方法通量低和/或预测性差。我们的目标是开发一个利用线虫进行药物筛选的简单且经济实惠的平台。在表达致病α-突触核蛋白的线虫中探索了PD治疗的“金标准”左旋多巴的效果。我们关注PD的两个关键特征：斑块形成和运动能力。与服用该药物的PD患者类似，接触左旋多巴改善了线虫的运动缺陷。此外，长期接触左旋多巴对寿命没有不利影响。这种基于线虫的方法用于筛选一系列小分子药物对α-突触核蛋白聚集和运动能力的影响，确定了几种值得进一步研究的有前景的化合物，最显著的是氨溴索。这种简单的方法意味着它可以在许多实验室中采用，以预先筛选对疾病进展有积极影响的候选化合物。
