Parkinson’s disease as a multisystem disorder: Whole transcriptome study in Parkinson’s disease patients’ skin and blood–finding the pathomechanistic link

Kurvits, L., Planken, A., Kadastik-Eerme, L., Reimann, E., Kingo, K., Kõks, S. and Taba, P. (2018) Parkinson’s disease as a multisystem disorder: Whole transcriptome study in Parkinson’s disease patients’ skin and blood–finding the pathomechanistic link. European Journal of Neurology, 25 . p. 126.

Abstract

Background and aims: Next to characteristic motor triad of Parkinson’s Disease (PD) due to loss of nigrostriatal neurons, more symptoms associated with non-neuronal tissues are emerging. Little is known about the molecular alterations underlying dermatologic issues or epidemiologic associations like increased incidence of melanoma in PD. The aim is to give an overview of the altered gene expression profiles of PD skin and blood using the novel method of RNA Sequencing. Networks of different genes are analyzed to map affected pathways that contribute to pathomolecular mechanism of PD in the periphery.

Methods: Whole transcriptomic profiling of 12+12 idiopathic PD patients’ and matched controls’ skin biopsies and venous whole blood was performed with highthroughput RNA-sequencing analysis. Followingly, pathway analysis of differentially changed gene expressions was performed. The results were validated using RT-qPCR.

Results: PD skin RNA-Seq resulted in a large collection of over 1000 differentially expressed genes, among which a clear pattern of global downregulation appeared. In blood, the differential changes were more subtle, blood being a heterogenous tissue. Pathways associated with mitochondrial metabolism and protein degradation by the ubiquitin-proteasome system were dysregulated in both.

Conclusion: The concordance of these results with previous gene expression profiling studies demonstrate that the molecular alterations in PD leading to neurodegeneration in the CNS are systemic and manifest also in peripheral tissues. Major affected pathways include dysfunction in protein metabolism, mitochondrial dysfunction and impaired immune system. Homeostatic imbalance in the skin can lead to increased susceptibility to mutagenic hazards and provide a possible molecular link between melanoma and PD.

Item Type:	Journal Article
Publisher:	Wiley
Copyright:	© 2018 EAN
Other Information:	Special Issue: Abstracts of the 4th Congress of the European Academy of Neurology, Lisbon, Portugal, June 2018
URI:	http://researchrepository.murdoch.edu.au/id/eprint/50916

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