Chemical Biology of Natural Products on Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a chronic and slowly progressive ageing-related neurodegenerative disorder that arises from interactions between environmental risk factors and genetic predispositions. This multifactorial aspect of the disease makes it difficult to find a therapy that benefits patients. There is currently no cure for PD. Even though, their use has decreased in the last two decades, natural products (NPs) remain a rich source of lead compounds for drug discovery. Here, we developed an unbiased multidimensional profiling method to examine the activity of a set of 590 pure NPs on human olfactory neurosphere-derived (hONS) cells from a PD patient. The biological profile of NPs was examined using multiparametric analysis to investigate known cellular pathways and organelles implicated in PD such as mitochondria, lysosomes, endosomes, apoptosis and autophagy. By targeting several cell components simultaneously we increased the chance of finding a phenotypic response. The compounds were then clustered based on their biological signature. The multidimensional phenotypic screening showed that all NPs, in our screening set, showed at least one phenotypic response on our cell model. This study provides evidence that natural products occupy biological relevant space.