Targeting polyamines and polyamine transport in Parkinson’s disease and beyond

Hosts: Esther Sammler and Dario Alessi

Venue: MSI Small Lecture Theatre, SLS

Abstract:

Parkinson’s disease is one of the most frequent neurodegenerative diseases. While the root cause and molecular mechanisms underlying Parkinson’s disease remain incompletely understood, lysosomal dysfunction is critically disturbed, which contributes to the accumulation of proteins and defective mitochondria. Our lab is specialized in the study of endolysosomal polyamine transporters, such as ATP13A2 (PARK9), which has been genetically linked with Parkinson’s disease. Our research revealed that ATP13A2 transports polyamines out of the lysosome, contributing to lysosomal and mitochondrial health. Our work in the Aligning Science Across Parkinson’s program demonstrated that a disturbed polyamine homeostasis affects Parkinson’s disease symptoms and that polyamines modulate Parkinson’s disease pathways. Furthermore, our molecular insights into the regulation of ATP13A2 have offered new therapeutic opportunities for Parkinson’s disease, which we actively pursue. Finally, we have also characterized the closely related polyamine transporters ATP13A3 and ATP13A4, which we propose as new drug targets for cancer.

Bio:

Positions

2012-present: Group Leader of the Laboratory of Cellular Transport System, KU Leuven, Belgium 

2020-present: Professor at the Faculty of Medicine, KU Leuven, Belgium

2018-2020: Associate Professor at the Faculty of Medicine, KU Leuven, Belgium

2011-2018: Assistant Professor – Tenure Track at the Faculty of Medicine, KU Leuven, Belgium

Awards

2018: Ernest-Solvay Award for Neurosciences (25,000 €)

2020: Achievement Award Valine de Spoelberch - Queen Elisabeth Medical Foundation of Neurosciences (100,000 €)

Selected References

1. ATP13A2 deficiency disrupts lysosomal polyamine export. van Veen S, Martin S, Van den Haute C, Benoy V, Lyons J, Vanhoutte R, Kahler JP, Decuypere JP, Gelders G, Lambie E, Zielich J, Swinnen JV, Annaert W, Agostinis P, Ghesquière B, Verhelst S, Baekelandt V, Eggermont J, Vangheluwe P. Nature. 2020 Jan 29, 578, 419–424. doi: 10.1038/s41586-020-1968-7. (IF 43.07)        
2. ATP13A2-mediated endo-lysosomal polyamine export counters mitochondrial oxidative stress. Vrijsen S, Besora-Casals L, van Veen S, Zielich J, Van den Haute C, Hamouda NN, Fischer C, Ghesquière B, Tournev I, Agostinis P, Baekelandt V, Eggermont J, Lambie E, Martin S, Vangheluwe P. Proc Natl Acad Sci U S A. 2020 Dec 8;117(49):31198-31207. doi: 10.1073/pnas.1922342117.
3. The polyamine transporter ATP13A3 mediates DFMO-induced polyamine uptake in neuroblastoma. Mujahid Azfar, Weiman Gao, Chris Van den Haute, Lin Xiao, Mawar Karsa, Ruby Pandher, Emma Ronca, Angelika Bongers, Ayu Karsa, Dayna Spurling, Xinyi Guo, Chelsea Mayoh, Mark R. Burns, Steven H.L. Verhelst, Murray D. Norris, Michelle Haber, Peter Vangheluwe, Klaartje Somers. bioRxiv 2024.02.20.581161; doi: https://doi.org/10.1101/2024.02.20.581161
4. ATP13A4 Upregulation Drives the Elevated Polyamine Transport System in the Breast Cancer Cell Line MCF7. van Veen S, Kourti A, Ausloos E, Van Asselberghs J, Van den Haute C, Baekelandt V, Eggermont J, Vangheluwe P. Biomolecules. 2023 May 31;13(6):918. doi: 10.3390/biom13060918.
5. ATP13A3 Variants Promote Pulmonary Arterial Hypertension by Disrupting Polyamine Transport. Bin Liu, Mujahid Azfar, Ekaterina Legchenko, James A. West, Shaun Martin, Chris Van den Haute, Veerle Baekelandt, John Wharton, Luke Howard, Martin R. Wilkins, Peter Vangheluwe, Nicholas W. Morrell, Paul D. Upton. bioRxiv 2023.08.29.554603; doi: https://doi.org/10.1101/2023.08.29.554603