15.06.2021 - 12:00
On 15 June at 12:00 Lille Kurvits will defend her doctoral thesis “Parkinson’s disease as a multisystem disorder: whole transcriptome study in Parkinson’s disease patients’ skin and blood”.
Professor Pille Taba, University of Tartu
Professor Sulev Kõks, University of Tartu/Murdoch University (Australia)
Research Fellow Anu Planken, University of Tartu
Professor Christine Klein, University of Luebeck/University Hospital Schleswig-Holstein (Germany)
Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease with a diagnostic complexity as there are currently no reliable biomarkers for PD. PD is a movement disorder characterized by slowness of voluntary movement (bradykinesia), rigidity and resting tremor. The pathophysiology of PD converges into pathognomonic loss of dopaminergic neurons in substantia nigra of the central nervous system and the accumulation of pathologic protein α-synuclein into Lewy bodies in neurons. Most PD cases are sporadic and large genome wide association studies show that gene variance alone is not the main cause of PD occurrence. This work, therefore, investigates gene expression (transcriptomics) of PD in search of feasible diagnostic and prognostic biomarkers. The tissue which the sample is taken from is relevant in transcriptomics, because gene expression is tissue specific. PD has canonically seen as a disease of the dopaminergic neurons in the central nervous tissue, but this tissue cannot be sampled from living patients. It is, therefore, necessary to find other tissues that allow sampling in vivo for biomarker research. A potential tissue of interest is the skin because PD patients have more melanoma and other specific skin conditions compared to the general population. Another promising tissue next to skin is the blood, because it is the easiest to sample and circulating the whole organism carries a lot of systemic information. The current work profiles gene expression from skin and blood using RNA sequencing in order to explore the disease specific involvement of nonneuronal peripheral tissues in PD. The results from PD skin show a pattern of global downregulation of differentially expressed genes that mirrors the pathophysiology of PD in the brain. Changes that lead to vulnerability in PD skin to mutagenic hazards are also mapped that might explain the epidemiologically observed elevated prevalence of melanoma in PD patients. This suggests that gene expression in the skin, a peripheral nonneuronal tissue, is PD-specifically changed. The results from PD blood show notably fewer changes, however, most are previously described in PD. This highlights the difficulty in using blood for biomarker discovery as the tissue is heterogeneous and the results are not easily reproducible. No overlapping differentially changed gene expressions are found in comparison of the two tissues in PD, which underlines the importance of tissue specific differences in gene expression. The study highlights notable differential gene expressions that show most robust changes and warrant further functional studies to evaluate their biomarker potential.
Ravila 19-1006 or via videobridge