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Review
. 2019 Apr 30;10(6):867-879.
doi: 10.1039/c9md00099b. eCollection 2019 Jun 1.

Using Drosophila as a platform for drug discovery from natural products in Parkinson's disease

Urmila Maitra  1 , Lukasz Ciesla  2
Affiliations
Review

Using Drosophila as a platform for drug discovery from natural products in Parkinson's disease

Urmila Maitra et al. Medchemcomm. .

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder with no cure. Despite intensive research, most of the currently available therapies are only effective in alleviating symptoms with no effect on disease progression. There is an urgent need for new therapeutics to impede disease progression. Natural products are valuable sources of bioactive compounds that can be exploited for novel therapeutic potential in PD pathogenesis. However, rapid screening of plant-derived natural products and characterization of bioactive compounds is costly and challenging. Drosophila melanogaster, commonly known as the fruit fly, has recently emerged as an excellent model for human neurodegenerative diseases, including PD. The high degree of conserved molecular pathways with mammalian models make Drosophila PD models an inexpensive solution to preliminary phases of target validation in the drug discovery pipeline. The present review provides an overview of drug discovery from natural extracts using Drosophila as a screening platform to evaluate the therapeutic potential of phytochemicals against PD.

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Figures

Fig. 1
Fig. 1. Structures of selected polyphenolic compounds proven to bind to multiple protein targets and often considered in medicinal chemistry literature as pan-assay interference compounds (PAINS).
Fig. 2
Fig. 2. The xenohormesis hypothesis. Adaptive stress response pathways in heterotrophs are activated by chemical cues produced by autotrophs and increase heterotrophs survival. Reproduced from ref. 30 with permission from John Wiley and Sons, Jul 16 2004.
Fig. 3
Fig. 3. Structure of ursolic acid, a pentacyclic triterpenoid molecule, recently found to regulate age and longevity by influencing the activity of SIRT1.
Fig. 4
Fig. 4. Examples of selected natural compounds and their derivatives identified as geroprotectors and geroneuroprotectors.
Fig. 5
Fig. 5. Structures of selected natural noxious chemicals which elicit hormetic neurobiological response and play a role of feeding deterrents.
Fig. 6
Fig. 6. Simplified model of evolutionary biochemical changes during co-evolution of plant and herbivores/omnivores. Reproduced from ref. 47 with permission from Elsevier, Oct 1 2015.
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