Neuronal Exosomal miRNA (N-ExRNAs) as Potential Biomarkers for Parkinson’s Disease
Open Access
- Author:
- Ebanks, Shauna A
- Graduate Program:
- Neuroscience
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- August 13, 2018
- Committee Members:
- Xuemei Huang, PhD, Thesis Advisor/Co-Advisor
Yuka Imamura, PhD, Committee Member
Kent Eugene Vrana, PhD, Committee Member
James Robert Connor, PhD, Committee Member - Keywords:
- MicroRNA
exosomes
Parkinson’s disease
biomarker
neurodegenerative diseases
next generation sequencing
clinical applications
Exosomes
microRNA - Abstract:
- Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer’s. PD is characterized clinically by motor dysfunction, and pathologically by dopamine neuron loss in the substantia nigra of the basal ganglia and the presence of Lewy bodies. The exact pathoetiology and pathogenesis of PD is unknown. The clinical diagnosis of PD relies entirely on neurological findings and the medical history of the patient. Currently, one of the major challenges in studying this progressive neurodegenerative disorder is to identify and develop biomarkers that will aid in the understanding and development of a PD therapy. This will aid clinicians in early stage disease diagnosis for disease management and monitoring of the disease progression. Exosomes, which are nanoscale extracellular vesicles secreted by most cell types, have shown potential to identify biochemical changes in the brain. They encapsulate various biomolecules including microRNA (miRNA), a class of small, non- coding RNAs that regulate protein levels post-transcriptionally. miRNA expression has become a prominent biomarker for a wide variety of diseases including PD and other neurodegenerative disorders. Previous studies only focused on expression profiling of miRNA in whole blood or circulating (cell-free) serum or plasma. This may not be the optimal miRNA source due to baseline contributions of irrelevant cells such as platelets or red/white blood cells or possible degradation of miRNA. Therefore, we hypothesized that the immunoenrichment of exosomes by a neuronal cell adhesion molecule, CD171, might be beneficial in enriching exosomes of neuronal origin which will allow us to get a more efficacious measure of miRNA biomarkers for PD patients compared to controls. We aimed to develop a robust exosome-miRNA profiling method by enriching neuronal origin exosomes using neuronal marker, CD171. Differentially expressed miRNAs were analyzed in 60 PD patients and 40 age- and gender-matched healthy volunteers to develop a candidate biomarker panel. Seventeen (17) miRNAs were significantly up regulated (q-value<0.05) and many were consistent with previous studies. Identification of these non-invasive biomarkers could potentially enhance PD diagnosis and help clinicians with early treatment intervention.