Converging peripheral blood microRNA profiles in Parkinson's disease and progressive supranuclear palsy

Lukas Pavelka*, Armin Rauschenberger, Ahmed Hemedan, Marek Ostaszewski, Enrico Glaab, Rejko Krüger*, Geeta Acharya, Gloria Aguayo, Myriam Alexandre, Muhammad Ali, Wim Ammerlann, Rudi Balling, Michele Bassis, Katy Beaumont, Regina Becker, Camille Bellora, Guy Berchem, Daniela Berg, Alexandre Bisdorff, Kathrin BrockmannJessica Calmes, Lorieza Castillo, Gessica Contesotto, Giuseppe Arena, Nico Diederich, Rene Dondelinger, Daniela Esteves, Guy Fagherazzi, Jean Yves Ferrand, Manon Gantenbein, Thomas Gasser, Piotr Gawron, Soumyabrata Ghosh, Marijus Giraitis, Enrico Glaab, Clarissa Gomes, Elisa Gómez De Lope, Jérôme Graas, Mariella Graziano, Valentin Groues, Anne Grünewald, Wei Gu, Gaël Hammot, Anne Marie Hanff, Linda Hansen, Maxime Hansen, Michael Heneka, Estelle Henry, Sylvia Herbrink, Sascha Herzinger, Michael Heymann, Michele Hu, Alexander Hundt, Ivana Paccoud, Nadine Jacoby, Jacek Jaroslaw Lebioda, Yohan Jaroz, Quentin Klopfenstein, Jochen Klucken, Rejko Krüger*, Pauline Lambert, Zied Landoulsi, Roseline Lentz, Inga Liepelt, Robert Liszka, Laura Longhino, Victoria Lorentz, Paula Cristina Lupu, Clare MacKay, Walter Maetzler, Katrin Marcus, Guilherme Marques, Tainá Marques, Patricia Martins Conde, Patrick May, Deborah McIntyre, Chouaib Mediouni, Francoise Meisch, Myriam Menster, Maura Minelli, Michel Mittelbronn, Brit Mollenhauer, Carlos Moreno, Friedrich Mühlschlegel, Romain Nati, Ulf Nehrbass, Sarah Nickels, Beatrice Nicolai, Jean Paul Nicolay, Fozia Noor, Marek Ostaszewski, Sinthuja Paccontrolshek, Claire Pauly, Laure Pauly, Lukas Pavelka*, Magali Perquin, Rosalina Ramos Lima, Armin Rauschenberger, Rajesh Rawal, Dheeraj Reddy Bobbili, Eduardo Rosales, Isabel Rosety, Kirsten Rump, Estelle Sandt, Stefano Sapienza, Venkata Satagopam, Margaux Schmitt, Sabine Schmitz, Reinhard Schneider, Jens Schwamborn, Jean Edouard Schweitzer, Amir Sharify, Ekaterina Soboleva, Kate Sokolowska, Olivier Terwindt, Hermann Thien, Elodie Thiry, Rebecca Ting Jiin Loo, Christophe Trefois, Johanna Trouet, Olena Tsurkalenko, Michel Vaillant, Mesele Valenti, Sijmen Van Schagen, Liliana Vilas Boas, Maharshi Vyas, Richard Wade-Martins, Paul Wilmes, Evi Wollscheid-Lengeling, Gelani Zelimkhanov

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

Abstract

MicroRNAs act via targeted suppression of messenger RNA translation in the DNA-RNA-protein axis. The dysregulation of microRNA(s) reflects the epigenetic changes affecting the cellular processes in multiple disorders. To understand the complex effect of dysregulated microRNAs linked to neurodegeneration, we performed a cross-sectional microRNA expression analysis in idiopathic Parkinson's disease (n = 367), progressive supranuclear palsy (n = 35) and healthy controls (n = 416) from the Luxembourg Parkinson's Study, followed by prediction modelling, enriched pathway analysis and target simulation of dysregulated microRNAs using probabilistic Boolean modelling. Forty-six microRNAs were identified to be dysregulated in Parkinson's disease versus controls and 16 in progressive supranuclear palsy versus controls with 4 overlapping significantly dysregulated microRNAs between the comparisons. Predictive power of microRNA subsets (including up to 100 microRNAs) was modest for differentiating Parkinson's disease or progressive supranuclear palsy from controls (maximal cross-validated area under the receiver operating characteristic curve 0.76 and 0.86, respectively) and low for progressive supranuclear palsy versus Parkinson's disease (maximal cross-validated area under the receiver operating characteristic curve 0.63). The enriched pathway analysis revealed natural killer cell pathway to be dysregulated in both, Parkinson's disease and progressive supranuclear palsy versus controls, indicating that the immune system might play an important role in both diseases. Probabilistic Boolean modelling of pathway dynamics affected by dysregulated microRNAs in Parkinson's disease and progressive supranuclear palsy revealed partially overlapping dysregulation in activity of the transcription factor EB, endoplasmic reticulum stress signalling, calcium signalling pathway, dopaminergic transcription and peroxisome proliferator-activated receptor gamma coactivator-1α activity, though involving different mechanisms. These findings indicated a partially convergent (sub)cellular end-point dysfunction at multiple levels in Parkinson's disease and progressive supranuclear palsy, but with distinctive underlying molecular mechanisms.

Original languageEnglish
Article numberfcae187
JournalBrain communications
Volume6
Issue number3
DOIs
Publication statusPublished - 31 May 2024

Keywords

  • Boolean modelling
  • microRNA
  • natural killer cell
  • Parkinson's disease
  • progressive supranuclear palsy

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