This is a snippet of some of the latest research conducted in Miguel’s lab at the MRC Toxicology Unit.
In Miguel’s lab, we use the fruit fly to model human diseases such as Parkinson’s disease.
A good article on the power of this model system can be found here. We are investigating a particular fly model of Parkinson’s disease linked to mutations in a human gene called PARKIN. Fruit flies also contain a Parkin gene in their DNA and we have in the lab flies that are mutated in this gene. It turns out that these flies lose the same type of neurons that are lost in Parkinson’s disease patients (dopaminergic neurons) in their brains when they age. This loss is detected in a particular cluster of dopaminergic neurons called the protocerebral posterior lateral 1 cluster (PPL1). The lifespan of these flies is much shorter than humans. An old fruit fly means a fly that is about 1 month old!
In a study we published in Cell Death and Disease (here is a link to this study), a peer-reviewed scientific journal, we explored the alterations in the metabolism of parkin mutant flies and found that they were lacking certain vitamin precursors. This is probably a consequence of the lack of functional parkin, a molecule involved in maintaining viable mitochondria, the cells’s power generators.
When parkin mutants were fed with a diet supplemented with nicotinamide (NAM), the dopaminergic neuron loss was abolished (see figure above). This suggests that NAM, when fed to flies before they loose dopaminergic neurons, is neuroprotective. However, one should remember Parkinson’s patients have already lost a large number of dopaminergic neurons when they are diagnosed. Therefore, we cannot say that vitamin B3 derivatives would actually work after the neuronal loss has already occurred.
In our lab, we are now investigating if such vitamin supplements have any beneficial effects in parkin flies after the neuronal loss has already happened.
This research is an example of the use of basic science employing a simple model organism to discover possible therapeutic approaches for diseases such as Parkinson’s.