Pharmacological LRRK2 kinase inhibition induces LRRK2 protein destabilization and proteasomal degradation
Identifieur interne : 000197 ( Main/Exploration ); précédent : 000196; suivant : 000198Pharmacological LRRK2 kinase inhibition induces LRRK2 protein destabilization and proteasomal degradation
Auteurs : E. Lobbestael [Belgique] ; L. Civiero [Italie] ; T. De Wit [Belgique] ; J.-M. Taymans [France] ; E. Greggio [Italie] ; V. Baekelandt [Belgique]Source :
- Scientific Reports [ 2045-2322 ] ; 2016.
Abstract
Leucine-rich repeat kinase 2 (LRRK2) kinase activity is increased in several pathogenic mutations, including the most common mutation, G2019S, and is known to play a role in Parkinson’s disease (PD) pathobiology. This has stimulated the development of potent, selective LRRK2 kinase inhibitors as one of the most prevailing disease-modifying therapeutic PD strategies. Although several lines of evidence support beneficial effects of LRRK2 kinase inhibitors, many questions need to be answered before clinical applications can be envisaged. Using six different LRRK2 kinase inhibitors, we show that LRRK2 kinase inhibition induces LRRK2 dephosphorylation and can reduce LRRK2 protein levels of overexpressed wild type and G2019S, but not A2016T or K1906M, LRRK2 as well as endogenous LRRK2 in mouse brain, lung and kidney. The inhibitor-induced reduction in LRRK2 levels could be reversed by proteasomal inhibition, but not by lysosomal inhibition, while mRNA levels remained unaffected. In addition, using LRRK2 S910A and S935A phosphorylation mutants, we show that dephosphorylation of these sites is not required for LRRK2 degradation. Increasing our insight in the molecular and cellular consequences of LRRK2 kinase inhibition will be crucial in the further development of LRRK2-based PD therapies.
Url:
DOI: 10.1038/srep33897
PubMed: 27658356
PubMed Central: 5034242
Affiliations:
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Lobbestael</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven</institution>, Kapucijnenvoer 33, 3000 Leuven,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Civiero, L" sort="Civiero, L" uniqKey="Civiero L" first="L." last="Civiero">L. Civiero</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Biology, University of Padova</institution>, 35131 Padova,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="De Wit, T" sort="De Wit, T" uniqKey="De Wit T" first="T." last="De Wit">T. De Wit</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven</institution>, Kapucijnenvoer 33, 3000 Leuven,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Taymans, J M" sort="Taymans, J M" uniqKey="Taymans J" first="J.-M." last="Taymans">J.-M. Taymans</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>UMR-S1172 Jean-Pierre Aubert Research Center – (INSERM - CHRU de Lille - Université de Lille), Early Stages of Parkinson’s Disease Team</institution>, Lille,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Greggio, E" sort="Greggio, E" uniqKey="Greggio E" first="E." last="Greggio">E. Greggio</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Biology, University of Padova</institution>, 35131 Padova,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Baekelandt, V" sort="Baekelandt, V" uniqKey="Baekelandt V" first="V." last="Baekelandt">V. Baekelandt</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven</institution>, Kapucijnenvoer 33, 3000 Leuven,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Leucine-rich repeat kinase 2 (LRRK2) kinase activity is increased in several pathogenic mutations, including the most common mutation, G2019S, and is known to play a role in Parkinson’s disease (PD) pathobiology. This has stimulated the development of potent, selective LRRK2 kinase inhibitors as one of the most prevailing disease-modifying therapeutic PD strategies. Although several lines of evidence support beneficial effects of LRRK2 kinase inhibitors, many questions need to be answered before clinical applications can be envisaged. Using six different LRRK2 kinase inhibitors, we show that LRRK2 kinase inhibition induces LRRK2 dephosphorylation and can reduce LRRK2 protein levels of overexpressed wild type and G2019S, but not A2016T or K1906M, LRRK2 as well as endogenous LRRK2 in mouse brain, lung and kidney. The inhibitor-induced reduction in LRRK2 levels could be reversed by proteasomal inhibition, but not by lysosomal inhibition, while mRNA levels remained unaffected. In addition, using LRRK2 S910A and S935A phosphorylation mutants, we show that dephosphorylation of these sites is not required for LRRK2 degradation. Increasing our insight in the molecular and cellular consequences of LRRK2 kinase inhibition will be crucial in the further development of LRRK2-based PD therapies.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Taymans, J M" uniqKey="Taymans J">J. M. Taymans</name></author><author><name sortKey="Greggio, E" uniqKey="Greggio E">E. Greggio</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gasser, T" uniqKey="Gasser T">T. Gasser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Paisan Ruiz, C" uniqKey="Paisan Ruiz C">C. Paisan-Ruiz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lill, C M" uniqKey="Lill C">C. M. Lill</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ross, O A" uniqKey="Ross O">O. A. Ross</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Satake, W" uniqKey="Satake W">W. Satake</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simon Sanchez, J" uniqKey="Simon Sanchez J">J. Simon-Sanchez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Greggio, E" uniqKey="Greggio E">E. Greggio</name></author><author><name sortKey="Cookson, M R" uniqKey="Cookson M">M. R. Cookson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reynolds, A" uniqKey="Reynolds A">A. Reynolds</name></author><author><name sortKey="Doggett, E A" uniqKey="Doggett E">E. A. Doggett</name></author><author><name sortKey="Riddle, S M" uniqKey="Riddle S">S. M. Riddle</name></author><author><name sortKey="Lebakken, C S" uniqKey="Lebakken C">C. S. Lebakken</name></author><author><name sortKey="Nichols, R J" uniqKey="Nichols R">R. J. Nichols</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sheng, Z" uniqKey="Sheng Z">Z. Sheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Greggio, E" uniqKey="Greggio E">E. Greggio</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, B D" uniqKey="Lee B">B. D. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, W W" uniqKey="Smith W">W. W. Smith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cooper, O" uniqKey="Cooper O">O. Cooper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yao, C" uniqKey="Yao C">C. Yao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deng, X" uniqKey="Deng X">X. Deng</name></author><author><name sortKey="Choi, H G" uniqKey="Choi H">H. G. Choi</name></author><author><name sortKey="Buhrlage, S J" uniqKey="Buhrlage S">S. J. Buhrlage</name></author><author><name sortKey="Gray, N S" uniqKey="Gray N">N. S. Gray</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kethiri, R R" uniqKey="Kethiri R">R. R. Kethiri</name></author><author><name sortKey="Bakthavatchalam, R" uniqKey="Bakthavatchalam R">R. Bakthavatchalam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gloeckner, C J" uniqKey="Gloeckner C">C. J. Gloeckner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nichols, R J" uniqKey="Nichols R">R. J. Nichols</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="West, A B" uniqKey="West A">A. B. West</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chia, R" uniqKey="Chia R">R. Chia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Doggett, E A" uniqKey="Doggett E">E. A. Doggett</name></author><author><name sortKey="Zhao, J" uniqKey="Zhao J">J. Zhao</name></author><author><name sortKey="Mork, C N" uniqKey="Mork C">C. N. Mork</name></author><author><name sortKey="Hu, D" uniqKey="Hu D">D. Hu</name></author><author><name sortKey="Nichols, R J" uniqKey="Nichols R">R. J. Nichols</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dzamko, N" uniqKey="Dzamko N">N. Dzamko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ito, G" uniqKey="Ito G">G. Ito</name></author><author><name sortKey="Fujimoto, T" uniqKey="Fujimoto T">T. Fujimoto</name></author><author><name sortKey="Kamikawaji, S" uniqKey="Kamikawaji S">S. Kamikawaji</name></author><author><name sortKey="Kuwahara, T" uniqKey="Kuwahara T">T. Kuwahara</name></author><author><name sortKey="Iwatsubo, T" uniqKey="Iwatsubo T">T. Iwatsubo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lobbestael, E" uniqKey="Lobbestael E">E. Lobbestael</name></author><author><name sortKey="Baekelandt, V" uniqKey="Baekelandt V">V. Baekelandt</name></author><author><name sortKey="Taymans, J M" uniqKey="Taymans J">J. M. Taymans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muda, K" uniqKey="Muda K">K. Muda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Choi, H G" uniqKey="Choi H">H. G. Choi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dzamko, N" uniqKey="Dzamko N">N. Dzamko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vancraenenbroeck, R" uniqKey="Vancraenenbroeck R">R. Vancraenenbroeck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hermanson, S B" uniqKey="Hermanson S">S. B. Hermanson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Delbroek, L" uniqKey="Delbroek L">L. Delbroek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lobbestael, E" uniqKey="Lobbestael E">E. Lobbestael</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Taymans, J M" uniqKey="Taymans J">J. M. Taymans</name></author><author><name sortKey="Baekelandt, V" uniqKey="Baekelandt V">V. Baekelandt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, J" uniqKey="Zhao J">J. Zhao</name></author><author><name sortKey="Molitor, T P" uniqKey="Molitor T">T. P. Molitor</name></author><author><name sortKey="Langston, J W" uniqKey="Langston J">J. W. Langston</name></author><author><name sortKey="Nichols, R J" uniqKey="Nichols R">R. J. Nichols</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fuji, R N" uniqKey="Fuji R">R. N. Fuji</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Herzig, M C" uniqKey="Herzig M">M. C. Herzig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Skibinski, G" uniqKey="Skibinski G">G. Skibinski</name></author><author><name sortKey="Nakamura, K" uniqKey="Nakamura K">K. Nakamura</name></author><author><name sortKey="Cookson, M R" uniqKey="Cookson M">M. R. Cookson</name></author><author><name sortKey="Finkbeiner, S" uniqKey="Finkbeiner S">S. Finkbeiner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fell, M J" uniqKey="Fell M">M. J. Fell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baptista, M A" uniqKey="Baptista M">M. A. Baptista</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miklavc, P" uniqKey="Miklavc P">P. Miklavc</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Daher, J P" uniqKey="Daher J">J. P. Daher</name></author><author><name sortKey="Volpicelli Daley, L A" uniqKey="Volpicelli Daley L">L. A. Volpicelli-Daley</name></author><author><name sortKey="Blackburn, J P" uniqKey="Blackburn J">J. P. Blackburn</name></author><author><name sortKey="Moehle, M S" uniqKey="Moehle M">M. S. Moehle</name></author><author><name sortKey="West, A B" uniqKey="West A">A. B. West</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, X" uniqKey="Lin X">X. Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Henderson, J L" uniqKey="Henderson J">J. L. Henderson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reith, A D" uniqKey="Reith A">A. D. Reith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deng, X" uniqKey="Deng X">X. Deng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ramsden, N" uniqKey="Ramsden N">N. Ramsden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nichols, R J" uniqKey="Nichols R">R. J. Nichols</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reith, A D" uniqKey="Reith A">A. D. Reith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name></author><author><name sortKey="Deng, X" uniqKey="Deng X">X. Deng</name></author><author><name sortKey="Choi, H G" uniqKey="Choi H">H. G. Choi</name></author><author><name sortKey="Alessi, D R" uniqKey="Alessi D">D. R. 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Herzig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tong, Y" uniqKey="Tong Y">Y. Tong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tong, Y" uniqKey="Tong Y">Y. Tong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Daher, J P L" uniqKey="Daher J">J. P. L. Daher</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Belgique</li><li>France</li><li>Italie</li></country></list><tree><country name="Belgique"><noRegion><name sortKey="Lobbestael, E" sort="Lobbestael, E" uniqKey="Lobbestael E" first="E." last="Lobbestael">E. Lobbestael</name></noRegion><name sortKey="Baekelandt, V" sort="Baekelandt, V" uniqKey="Baekelandt V" first="V." last="Baekelandt">V. Baekelandt</name><name sortKey="De Wit, T" sort="De Wit, T" uniqKey="De Wit T" first="T." last="De Wit">T. De Wit</name></country><country name="Italie"><noRegion><name sortKey="Civiero, L" sort="Civiero, L" uniqKey="Civiero L" first="L." last="Civiero">L. Civiero</name></noRegion><name sortKey="Greggio, E" sort="Greggio, E" uniqKey="Greggio E" first="E." last="Greggio">E. Greggio</name></country><country name="France"><noRegion><name sortKey="Taymans, J M" sort="Taymans, J M" uniqKey="Taymans J" first="J.-M." last="Taymans">J.-M. Taymans</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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