Neuron-restricted RNA Profiles in the Plasma of Those with Genetic and Sporadic Parkinson's Disease
Improved Biomarkers and Clinical Outcome Measures, 2017
MicroRNAs (miRs) are short RNA molecules (messengers that carry genetic information to DNA) that block protein expression by crossing with hundreds of mRNA targets. Neuron-restricted miRs regulate specific aspects of neuron development and function, unlike broadly expressed miRs that control house-keeping processes. Deregulation of neuron miR expression leads to brain dysfunction. Neuronal miRs are released to fluids outside the cell and are detected in considerable levels in the blood. We plan to measure the expression profile of neuronal miRs in a large population of those with genetic and idiopathic (unknown cause) Parkinson's disease (PD) to identify specific miR signatures of PD.
We predict that the levels of neuronal miRs released in blood by degenerating PD neurons are different from those of healthy neurons. We hypothesize that we can use these measures to differentiate those with PD from those without PD, as well as gain insights into the specific dysfunction of PD neurons.
We will isolate total miR from the blood of those with genetic (SNCA and GBA; two genetics mutation associated with PD) and idiopathic PD, as well as age/sex-matched healthy participants. Neuronal miRs levels will be measured using a method to amplify DNA materials and a panel of PD-predictive miRs will be developed. This miR panel will later be used to test another set of blood samples collected from those with PD and healthy participants during the course of this initial study.
Impact on Diagnosis/Treatment of Parkinson's disease:
Detection of deregulated neuronal miRs will point to specific dysfunction in neurons that will help researchers develop new treatments and will help clinicians tailor patient care according to available therapeutics. As a diagnostic tool, the miR panel may help categorize groups of those with PD based on similar molecular disruptions and monitor disease progression with minimal invasion at a low cost.
Next Steps for Development:
A panel of specific PD-predictive neuronal miRs will be constructed and will later be tested in a new group of PD participants to validate findings. Deregulated miRs will also be assessed for their role in neuronal function.
Professor of Neurology and Neurobiology at University of Athens Medical School and Biomedical Research Foundation of the Academy of Athens
Location: Athens, Greece
Assistant Professor at Biomedical Research Foundation, Academy of Athens
Location: Athens, Greece