THE NEUROEXPLORISTS
Visualising the invisible in Parkinson’s disease
Noelia Pelegrina-Hidalgo, Third-year PhD,
University of Edinburgh, UK
BACKGROUND:
Parkinson’s disease is the second most common neurodegenerative disease in the world affecting people’s lives drastically. Unfortunately, we don’t currently count with treatments for the disease, and once diagnosed, a high percentage of neurodegeneration has occurred (meaning a lot of neurones have irreversibly been lost). The main means of neurodegeneration in Parkinson’s disease has been attributed to ⍺-synuclein aggregation. In order to apply better therapies for the disease, it should be diagnosed earlier, however, it is very difficult for clinicians to know what is going in the brain from a distance. Here is when extracellular vesicles come into place, since they are parts of neurones that travel in our bloodstream and can act as windows into the physiology of neurones and their activity.
In my PhD project, I aim to develop a technique that could diagnose Parkinson’s at an earlier stage when it would be possible to use therapies that have not worked in later stages of the disease.
METHODOLOGY:
For this, I am planning to use blood-derived extracellular vesicles from neuronal origin to look at the proteins they carry within them, known as cargo. In order to do this, I use a specific type of imaging: super-resolution imaging, that allows us to visualise very small structures that fall below the diffraction limit of light. This means we can define biological processes that are smaller than 200 nm, overcoming traditional microscopy limit. This way, we can look into extracellular vesicles and identify ⍺- synuclein aggregates.
RESULTS:
So far, I have been able to image nematode-derived extracellular vesicles cargo (unpublished data). I have also imaged ⍺- synuclein fibrils (similar to those occurring in Parkinson's disease affected neurons) on the surface to show the resolution gained from imaging using super-resolution techniques.
Figure 1. ⍺-synuclein fibril imaged using traditional microscopy (left) and using super-resolution microscopy (middle). Merged image (right) shows higher details obtained from using high resolution imaging techniques.
FUTURE WORK:
My next steps are applying this technique to patient-derived extracellular vesicles to try and distinguish between disease and healthy control samples, confirming the technique works. It will require optimisation of the protocol to adapt to human biofluid-technique works. It will require optimisation of the protocol to adapt to human biofluid-derived samples and detection adjusting depending on concentrations of samples.
FUNDED BY:
Medical Research Scotland in partnership with ONI
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