{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:56:20Z","timestamp":1793228180035,"version":"4.5.0"},"reference-count":86,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T00:00:00Z","timestamp":1746835200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T00:00:00Z","timestamp":1746835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Parkinsons Dis."],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Amyloid aggregation is associated with neurodegenerative disease and its modulation is a focus of drug development. We developed a chemical proteomics pipeline to probe the mechanism of action of anti-amyloidogenic compounds. Our approach identifies putative interaction sites with high resolution, can probe compound interactions with specific target conformations and directly in cell and brain extracts, and identifies off-targets. We analysed interactions of six anti-amyloidogenic compounds and the amyloid binder Thioflavin T with different conformations of the Parkinson\u2019s disease protein \u03b1-Synuclein and tested specific compounds in cell or brain lysates. AC Immune compound 2 interacted with \u03b1-Synuclein in vitro, in intact neurons and in neuronal lysates, reduced neuronal \u03b1-Synuclein levels in a seeded model, and had protective effects. EGCG, Baicalein, ThT and doxycycline interacted with \u03b1-Synuclein in vitro but not substantially in cell lysates, with many additional putative targets, underscoring the importance of testing compounds in situ. Our pipeline will enable screening of compounds against any amyloidogenic proteins in cell and patient brain extracts and mechanistic studies of compound action.<\/jats:p>","DOI":"10.1038\/s41531-025-00966-5","type":"journal-article","created":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T12:37:12Z","timestamp":1746880632000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["An approach to characterize mechanisms of action of anti-amyloidogenic compounds in vitro and in situ"],"prefix":"10.1038","volume":"11","author":[{"given":"P.","family":"Stalder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3706-5911","authenticated-orcid":false,"given":"T.","family":"Serdiuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2087-8075","authenticated-orcid":false,"given":"D.","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Fleischmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Ait-Bouziad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.-P.","family":"Quast","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Malinovska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ouared","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Davranche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4868-3704","authenticated-orcid":false,"given":"W.","family":"Haenseler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7230-2380","authenticated-orcid":false,"given":"C.","family":"Boudou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Tsika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"St\u00f6hr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Melki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Riek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4109-3552","authenticated-orcid":false,"given":"P.","family":"Picotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,10]]},"reference":[{"key":"966_CR1","doi-asserted-by":"publisher","unstructured":"Otzen, D. & Riek, R. Functional amyloids. Cold Spring Harb. Perspect. Biol. 11. https:\/\/doi.org\/10.1101\/cshperspect.a033860 (2019).","DOI":"10.1101\/cshperspect.a033860"},{"key":"966_CR2","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/42166","volume":"388","author":"MG Spillantini","year":"1997","unstructured":"Spillantini, M. G. et al. Alpha-synuclein in Lewy bodies. Nature 388, 839\u2013840, https:\/\/doi.org\/10.1038\/42166 (1997).","journal-title":"Nature"},{"key":"966_CR3","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/s0006-291x(84)80190-4","volume":"120","author":"GG Glenner","year":"1984","unstructured":"Glenner, G. G. & Wong, C. W. Alzheimer\u2019s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 120, 885\u2013890, https:\/\/doi.org\/10.1016\/s0006-291x(84)80190-4 (1984).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"966_CR4","doi-asserted-by":"publisher","first-page":"8729","DOI":"10.1073\/pnas.82.24.8729","volume":"82","author":"CW Wong","year":"1985","unstructured":"Wong, C. W., Quaranta, V. & Glenner, G. G. Neuritic plaques and cerebrovascular amyloid in Alzheimer disease are antigenically related. Proc. Natl. Acad. Sci. USA 82, 8729\u20138732, https:\/\/doi.org\/10.1073\/pnas.82.24.8729 (1985).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"966_CR5","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/s1097-2765(02)00602-0","volume":"10","author":"A Lunkes","year":"2002","unstructured":"Lunkes, A. et al. Proteases acting on mutant huntingtin generate cleaved products that differentially build up cytoplasmic and nuclear inclusions. Mol. Cell 10, 259\u2013269, https:\/\/doi.org\/10.1016\/s1097-2765(02)00602-0 (2002).","journal-title":"Mol. Cell"},{"key":"966_CR6","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1016\/j.chembiol.2018.08.005","volume":"25","author":"M Kurnik","year":"2018","unstructured":"Kurnik, M. et al. Potent alpha-Synuclein aggregation inhibitors, identified by high-throughput screening, mainly target the monomeric state. Cell Chem. Biol. 25, 1389\u20131402.e1389, https:\/\/doi.org\/10.1016\/j.chembiol.2018.08.005 (2018).","journal-title":"Cell Chem. Biol."},{"key":"966_CR7","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/s42004-020-00412-y","volume":"3","author":"R Staats","year":"2020","unstructured":"Staats, R. et al. Screening of small molecules using the inhibition of oligomer formation in alpha-synuclein aggregation as a selection parameter. Commun. Chem. 3, 191, https:\/\/doi.org\/10.1038\/s42004-020-00412-y (2020).","journal-title":"Commun. Chem."},{"key":"966_CR8","doi-asserted-by":"publisher","first-page":"160696","DOI":"10.1098\/rsos.160696","volume":"4","author":"C Xue","year":"2017","unstructured":"Xue, C., Lin, T. Y., Chang, D. & Guo, Z. Thioflavin T as an amyloid dye: fibril quantification, optimal concentration and effect on aggregation. R. Soc. Open Sci. 4, 160696, https:\/\/doi.org\/10.1098\/rsos.160696 (2017).","journal-title":"R. Soc. Open Sci."},{"key":"966_CR9","doi-asserted-by":"publisher","first-page":"238","DOI":"10.2174\/138620708783877753","volume":"11","author":"H Varma","year":"2008","unstructured":"Varma, H., Lo, D. C. & Stockwell, B. R. High throughput screening for neurodegeneration and complex disease phenotypes. Comb. Chem. High. Throughput Screen 11, 238\u2013248, https:\/\/doi.org\/10.2174\/138620708783877753 (2008).","journal-title":"Comb. Chem. High. Throughput Screen"},{"key":"966_CR10","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/978-1-62703-342-8_6","volume":"993","author":"R Guha","year":"2013","unstructured":"Guha, R. On exploring structure-activity relationships. Methods Mol. Biol. 993, 81\u201394, https:\/\/doi.org\/10.1007\/978-1-62703-342-8_6 (2013).","journal-title":"Methods Mol. Biol."},{"key":"966_CR11","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1016\/j.csbj.2021.02.018","volume":"19","author":"V Temml","year":"2021","unstructured":"Temml, V. & Kutil, Z. Structure-based molecular modeling in SAR analysis and lead optimization. Comput. Struct. Biotechnol. J. 19, 1431\u20131444, https:\/\/doi.org\/10.1016\/j.csbj.2021.02.018 (2021).","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"966_CR12","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/s41586-020-2317-6","volume":"585","author":"M Schweighauser","year":"2020","unstructured":"Schweighauser, M. et al. Structures of alpha-synuclein filaments from multiple system atrophy. Nature 585, 464\u2013469, https:\/\/doi.org\/10.1038\/s41586-020-2317-6 (2020).","journal-title":"Nature"},{"key":"966_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12683-8","volume":"10","author":"M Kollmer","year":"2019","unstructured":"Kollmer, M. et al. Cryo-EM structure and polymorphism of Abeta amyloid fibrils purified from Alzheimer\u2019s brain tissue. Nat. Commun. 10, 4760, https:\/\/doi.org\/10.1038\/s41467-019-12683-8 (2019).","journal-title":"Nat. Commun."},{"key":"966_CR14","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/nature23002","volume":"547","author":"AWP Fitzpatrick","year":"2017","unstructured":"Fitzpatrick, A. W. P. et al. Cryo-EM structures of tau filaments from Alzheimer\u2019s disease. Nature 547, 185\u2013190, https:\/\/doi.org\/10.1038\/nature23002 (2017).","journal-title":"Nature"},{"key":"966_CR15","doi-asserted-by":"publisher","unstructured":"Zhang, W. et al. Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer\u2019s and Pick\u2019s diseases. Elife 8. https:\/\/doi.org\/10.7554\/eLife.43584 (2019).","DOI":"10.7554\/eLife.43584"},{"key":"966_CR16","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/s41586-018-0454-y","volume":"561","author":"B Falcon","year":"2018","unstructured":"Falcon, B. et al. Structures of filaments from Pick\u2019s disease reveal a novel tau protein fold. Nature 561, 137\u2013140, https:\/\/doi.org\/10.1038\/s41586-018-0454-y (2018).","journal-title":"Nature"},{"key":"966_CR17","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/s41586-019-1026-5","volume":"568","author":"B Falcon","year":"2019","unstructured":"Falcon, B. et al. Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules. Nature 568, 420\u2013423, https:\/\/doi.org\/10.1038\/s41586-019-1026-5 (2019).","journal-title":"Nature"},{"key":"966_CR18","doi-asserted-by":"publisher","first-page":"15345","DOI":"10.1074\/jbc.M111.318949","volume":"287","author":"B Fauvet","year":"2012","unstructured":"Fauvet, B. et al. alpha-Synuclein in central nervous system and from erythrocytes, mammalian cells, and Escherichia coli exists predominantly as disordered monomer. J. Biol. Chem. 287, 15345\u201315364, https:\/\/doi.org\/10.1074\/jbc.M111.318949 (2012).","journal-title":"J. Biol. Chem."},{"key":"966_CR19","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1042\/BST20120096","volume":"40","author":"A Binolfi","year":"2012","unstructured":"Binolfi, A., Theillet, F. X. & Selenko, P. Bacterial in-cell NMR of human alpha-synuclein: a disordered monomer by nature?. Biochem. Soc. Trans. 40, 950\u2013954, https:\/\/doi.org\/10.1042\/BST20120096 (2012).","journal-title":"Biochem. Soc. Trans."},{"key":"966_CR20","doi-asserted-by":"publisher","first-page":"13709","DOI":"10.1021\/bi961799n","volume":"35","author":"PH Weinreb","year":"1996","unstructured":"Weinreb, P. H., Zhen, W., Poon, A. W., Conway, K. A. & Lansbury, P. T. Jr NACP, a protein implicated in Alzheimer\u2019s disease and learning, is natively unfolded. Biochemistry 35, 13709\u201313715, https:\/\/doi.org\/10.1021\/bi961799n (1996).","journal-title":"Biochemistry"},{"key":"966_CR21","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/nature16531","volume":"530","author":"FX Theillet","year":"2016","unstructured":"Theillet, F. X. et al. Structural disorder of monomeric alpha-synuclein persists in mammalian cells. Nature 530, 45\u201350, https:\/\/doi.org\/10.1038\/nature16531 (2016).","journal-title":"Nature"},{"key":"966_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32951-4","volume":"13","author":"PM Seidler","year":"2022","unstructured":"Seidler, P. M. et al. Structure-based discovery of small molecules that disaggregate Alzheimer\u2019s disease tissue derived tau fibrils in vitro. Nat. Commun. 13, 5451, https:\/\/doi.org\/10.1038\/s41467-022-32951-4 (2022).","journal-title":"Nat. Commun."},{"key":"966_CR23","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1007\/s00401-021-02294-3","volume":"141","author":"Y Shi","year":"2021","unstructured":"Shi, Y. et al. Cryo-EM structures of tau filaments from Alzheimer\u2019s disease with PET ligand APN-1607. Acta Neuropathol. 141, 697\u2013708, https:\/\/doi.org\/10.1007\/s00401-021-02294-3 (2021).","journal-title":"Acta Neuropathol."},{"key":"966_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38537-y","volume":"14","author":"GE Merz","year":"2023","unstructured":"Merz, G. E. et al. Stacked binding of a PET ligand to Alzheimer\u2019s tau paired helical filaments. Nat. Commun. 14, 3048, https:\/\/doi.org\/10.1038\/s41467-023-38537-y (2023).","journal-title":"Nat. Commun."},{"key":"966_CR25","doi-asserted-by":"publisher","first-page":"8497","DOI":"10.1038\/s41467-024-52265-x","volume":"15","author":"P Kunach","year":"2024","unstructured":"Kunach, P. et al. Cryo-EM structure of Alzheimer\u2019s disease tau filaments with PET ligand MK-6240. Nat. Commun. 15, 8497 (2024).","journal-title":"Nat. Commun."},{"key":"966_CR26","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/nature07814","volume":"458","author":"D Sakakibara","year":"2009","unstructured":"Sakakibara, D. et al. Protein structure determination in living cells by in-cell NMR spectroscopy. Nature 458, 102\u2013105, https:\/\/doi.org\/10.1038\/nature07814 (2009).","journal-title":"Nature"},{"key":"966_CR27","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1038\/nbt.2999","volume":"32","author":"Y Feng","year":"2014","unstructured":"Feng, Y. et al. Global analysis of protein structural changes in complex proteomes. Nat. Biotechnol. 32, 1036\u20131044, https:\/\/doi.org\/10.1038\/nbt.2999 (2014).","journal-title":"Nat. Biotechnol."},{"key":"966_CR28","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/513481a","volume":"513","author":"J Baell","year":"2014","unstructured":"Baell, J. & Walters, M. A. Chemistry: chemical con artists foil drug discovery. Nature 513, 481\u2013483, https:\/\/doi.org\/10.1038\/513481a (2014).","journal-title":"Nature"},{"key":"966_CR29","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1093\/bioinformatics\/btr671","volume":"30","author":"Y Xiao","year":"2014","unstructured":"Xiao, Y. et al. A novel significance score for gene selection and ranking. Bioinformatics 30, 801\u2013807, https:\/\/doi.org\/10.1093\/bioinformatics\/btr671 (2014).","journal-title":"Bioinformatics"},{"key":"966_CR30","doi-asserted-by":"publisher","first-page":"11282","DOI":"10.1073\/pnas.90.23.11282","volume":"90","author":"K Ueda","year":"1993","unstructured":"Ueda, K. et al. Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proc. Natl. Acad. Sci. USA 90, 11282\u201311286, https:\/\/doi.org\/10.1073\/pnas.90.23.11282 (1993).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"966_CR31","doi-asserted-by":"publisher","first-page":"8637","DOI":"10.1073\/pnas.0712179105","volume":"105","author":"M Vilar","year":"2008","unstructured":"Vilar, M. et al. The fold of alpha-synuclein fibrils. Proc. Natl. Acad. Sci. USA 105, 8637\u20138642, https:\/\/doi.org\/10.1073\/pnas.0712179105 (2008).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"966_CR32","doi-asserted-by":"publisher","first-page":"15871","DOI":"10.1073\/pnas.0506109102","volume":"102","author":"H Heise","year":"2005","unstructured":"Heise, H. et al. Molecular-level secondary structure, polymorphism, and dynamics of full-length alpha-synuclein fibrils studied by solid-state NMR. Proc. Natl. Acad. Sci. USA 102, 15871\u201315876, https:\/\/doi.org\/10.1073\/pnas.0506109102 (2005).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"966_CR33","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.cell.2020.12.021","volume":"184","author":"V Cappelletti","year":"2021","unstructured":"Cappelletti, V. et al. Dynamic 3D proteomes reveal protein functional alterations at high resolution in situ. Cell 184, 545\u2013559.e522, https:\/\/doi.org\/10.1016\/j.cell.2020.12.021 (2021).","journal-title":"Cell"},{"key":"966_CR34","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1038\/s41594-022-00837-0","volume":"29","author":"MT Mackmull","year":"2022","unstructured":"Mackmull, M. T. et al. Global, in situ analysis of the structural proteome in individuals with Parkinson\u2019s disease to identify a new class of biomarker. Nat. Struct. Mol. Biol. 29, 978\u2013989, https:\/\/doi.org\/10.1038\/s41594-022-00837-0 (2022).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"966_CR35","doi-asserted-by":"publisher","first-page":"13321","DOI":"10.1073\/pnas.0604080103","volume":"103","author":"A Zhou","year":"2006","unstructured":"Zhou, A., Wei, Z., Read, R. J. & Carrell, R. W. Structural mechanism for the carriage and release of thyroxine in the blood. Proc. Natl. Acad. Sci. USA 103, 13321\u201313326, https:\/\/doi.org\/10.1073\/pnas.0604080103 (2006).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"966_CR36","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1038\/s41596-022-00771-x","volume":"18","author":"L Malinovska","year":"2023","unstructured":"Malinovska, L. et al. Proteome-wide structural changes measured with limited proteolysis-mass spectrometry: an advanced protocol for high-throughput applications. Nat. Protoc. 18, 659\u2013682, https:\/\/doi.org\/10.1038\/s41596-022-00771-x (2023).","journal-title":"Nat. Protoc."},{"key":"966_CR37","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1038\/nsmb.1437","volume":"15","author":"DE Ehrnhoefer","year":"2008","unstructured":"Ehrnhoefer, D. E. et al. EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Nat. Struct. Mol. Biol. 15, 558\u2013566, https:\/\/doi.org\/10.1038\/nsmb.1437 (2008).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"966_CR38","doi-asserted-by":"publisher","first-page":"26846","DOI":"10.1074\/jbc.M403129200","volume":"279","author":"M Zhu","year":"2004","unstructured":"Zhu, M. et al. The flavonoid baicalein inhibits fibrillation of alpha-synuclein and disaggregates existing fibrils. J. Biol. Chem. 279, 26846\u201326857, https:\/\/doi.org\/10.1074\/jbc.M403129200 (2004).","journal-title":"J. Biol. Chem."},{"key":"966_CR39","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s40478-016-0310-y","volume":"4","author":"L Tatenhorst","year":"2016","unstructured":"Tatenhorst, L. et al. Fasudil attenuates aggregation of alpha-synuclein in models of Parkinson\u2019s disease. Acta Neuropathol. Commun. 4, 39, https:\/\/doi.org\/10.1186\/s40478-016-0310-y (2016).","journal-title":"Acta Neuropathol. Commun."},{"key":"966_CR40","doi-asserted-by":"publisher","DOI":"10.1002\/bip.23117","volume":"109","author":"G Fusco","year":"2018","unstructured":"Fusco, G. et al. Molecular determinants of the interaction of EGCG with ordered and disordered proteins. Biopolymers 109, e23117. https:\/\/doi.org\/10.1002\/bip.23117 (2018).","journal-title":"Biopolymers"},{"key":"966_CR41","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1021\/bi020429y","volume":"42","author":"JC Kessler","year":"2003","unstructured":"Kessler, J. C., Rochet, J. C. & Lansbury, P. T. Jr The N-terminal repeat domain of alpha-synuclein inhibits beta-sheet and amyloid fibril formation. Biochemistry 42, 672\u2013678, https:\/\/doi.org\/10.1021\/bi020429y (2003).","journal-title":"Biochemistry"},{"key":"966_CR42","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1002\/brb3.86","volume":"2","author":"Y Izawa","year":"2012","unstructured":"Izawa, Y. et al. Role of C-terminal negative charges and tyrosine residues in fibril formation of alpha-synuclein. Brain Behav. 2, 595\u2013605, https:\/\/doi.org\/10.1002\/brb3.86 (2012).","journal-title":"Brain Behav."},{"key":"966_CR43","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.jmb.2008.08.039","volume":"383","author":"DP Hong","year":"2008","unstructured":"Hong, D. P., Fink, A. L. & Uversky, V. N. Structural characteristics of alpha-synuclein oligomers stabilized by the flavonoid baicalein. J. Mol. Biol. 383, 214\u2013223, https:\/\/doi.org\/10.1016\/j.jmb.2008.08.039 (2008).","journal-title":"J. Mol. Biol."},{"key":"966_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/srep41755","volume":"7","author":"F Gonzalez-Lizarraga","year":"2017","unstructured":"Gonzalez-Lizarraga, F. et al. Repurposing doxycycline for synucleinopathies: remodelling of alpha-synuclein oligomers towards non-toxic parallel beta-sheet structured species. Sci. Rep. 7, 41755. https:\/\/doi.org\/10.1038\/srep41755 (2017).","journal-title":"Sci. Rep."},{"key":"966_CR45","doi-asserted-by":"publisher","first-page":"7503","DOI":"10.1021\/ja3115696","volume":"135","author":"FL Palhano","year":"2013","unstructured":"Palhano, F. L., Lee, J., Grimster, N. P. & Kelly, J. W. Toward the molecular mechanism(s) by which EGCG treatment remodels mature amyloid fibrils. J. Am. Chem. Soc. 135, 7503\u20137510, https:\/\/doi.org\/10.1021\/ja3115696 (2013).","journal-title":"J. Am. Chem. Soc."},{"key":"966_CR46","doi-asserted-by":"publisher","first-page":"4351","DOI":"10.1021\/acschemneuro.0c00598","volume":"11","author":"Y Yao","year":"2020","unstructured":"Yao, Y., Tang, Y. & Wei, G. Epigallocatechin Gallate Destabilizes alpha-Synuclein Fibril by Disrupting the E46-K80 Salt-Bridge and Inter-protofibril Interface. ACS Chem. Neurosci. 11, 4351\u20134361, https:\/\/doi.org\/10.1021\/acschemneuro.0c00598 (2020).","journal-title":"ACS Chem. Neurosci."},{"key":"966_CR47","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1111\/cbdd.13067","volume":"91","author":"X Liu","year":"2018","unstructured":"Liu, X. et al. Influence of EGCG on alpha-synuclein (alphaS) aggregation and identification of their possible binding mode: A computational study using molecular dynamics simulation. Chem. Biol. Drug Des. 91, 162\u2013171, https:\/\/doi.org\/10.1111\/cbdd.13067 (2018).","journal-title":"Chem. Biol. Drug Des."},{"key":"966_CR48","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.ijbiomac.2022.08.088","volume":"220","author":"Y Yao","year":"2022","unstructured":"Yao, Y., Tang, Y., Zhou, Y., Yang, Z. & Wei, G. Baicalein exhibits differential effects and mechanisms towards disruption of alpha-synuclein fibrils with different polymorphs. Int J. Biol. Macromol. 220, 316\u2013325, https:\/\/doi.org\/10.1016\/j.ijbiomac.2022.08.088 (2022).","journal-title":"Int J. Biol. Macromol."},{"key":"966_CR49","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2021.105256","volume":"151","author":"A Dominguez-Meijide","year":"2021","unstructured":"Dominguez-Meijide, A. et al. Doxycycline inhibits alpha-synuclein-associated pathologies in vitro and in vivo. Neurobiol. Dis. 151, 105256, https:\/\/doi.org\/10.1016\/j.nbd.2021.105256 (2021).","journal-title":"Neurobiol. Dis."},{"key":"966_CR50","doi-asserted-by":"publisher","unstructured":"Roy, D., Bhattacharyya, D. & Bhunia, A.. Do Catechins (ECG and EGCG) Bind to the Same Site as Thioflavin T (ThT) in Amyloid Fibril? Answer From Saturation Transfer Difference NMR. Nat. Prod. Commun. 14. https:\/\/doi.org\/10.1177\/1934578x19849791. (2019).","DOI":"10.1177\/1934578x19849791"},{"key":"966_CR51","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1016\/j.bbapap.2010.04.001","volume":"1804","author":"M Biancalana","year":"2010","unstructured":"Biancalana, M. & Koide, S. Molecular mechanism of Thioflavin-T binding to amyloid fibrils. Biochim. Biophys. Acta 1804, 1405\u20131412, https:\/\/doi.org\/10.1016\/j.bbapap.2010.04.001 (2010).","journal-title":"Biochim. Biophys. Acta"},{"key":"966_CR52","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1016\/j.procbio.2011.02.010","volume":"46","author":"N Sarkar","year":"2011","unstructured":"Sarkar, N., Kumar, M. & Dubey, V. K. Exploring possibility of promiscuity of amyloid inhibitor: studies on effect of selected compounds on folding and amyloid formation of proteins. Process Biochem. 46, 1179\u20131185 (2011).","journal-title":"Process Biochem."},{"key":"966_CR53","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1016\/j.freeradbiomed.2008.07.023","volume":"45","author":"T Ishii","year":"2008","unstructured":"Ishii, T. et al. Covalent modification of proteins by green tea polyphenol (-)-epigallocatechin-3-gallate through autoxidation. Free Radic. Biol. Med. 45, 1384\u20131394, https:\/\/doi.org\/10.1016\/j.freeradbiomed.2008.07.023 (2008).","journal-title":"Free Radic. Biol. Med."},{"key":"966_CR54","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.1021\/cb500086e","volume":"9","author":"HI Ingolfsson","year":"2014","unstructured":"Ingolfsson, H. I. et al. Phytochemicals perturb membranes and promiscuously alter protein function. ACS Chem. Biol. 9, 1788\u20131798, https:\/\/doi.org\/10.1021\/cb500086e (2014).","journal-title":"ACS Chem. Biol."},{"key":"966_CR55","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/s0014-5793(01)03115-5","volume":"509","author":"GK Tofaris","year":"2001","unstructured":"Tofaris, G. K., Layfield, R. & Spillantini, M. G. alpha-synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome. FEBS Lett. 509, 22\u201326, https:\/\/doi.org\/10.1016\/s0014-5793(01)03115-5 (2001).","journal-title":"FEBS Lett."},{"key":"966_CR56","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.jneumeth.2015.11.009","volume":"261","author":"F Macchi","year":"2016","unstructured":"Macchi, F. et al. High-content analysis of alpha-synuclein aggregation and cell death in a cellular model of Parkinson\u2019s disease. J. Neurosci. Methods 261, 117\u2013127, https:\/\/doi.org\/10.1016\/j.jneumeth.2015.11.009 (2016).","journal-title":"J. Neurosci. Methods"},{"key":"966_CR57","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18071-x","volume":"11","author":"I Piazza","year":"2020","unstructured":"Piazza, I. et al. A machine learning-based chemoproteomic approach to identify drug targets and binding sites in complex proteomes. Nat. Commun. 11, 4200. https:\/\/doi.org\/10.1038\/s41467-020-18071-x (2020).","journal-title":"Nat. Commun."},{"key":"966_CR58","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1016\/j.chembiol.2018.09.010","volume":"25","author":"JD Mortison","year":"2018","unstructured":"Mortison, J. D. et al. Tetracyclines modify translation by targeting key human rRNA Substructures. Cell Chem. Biol. 25, 1506\u20131518.e1513, https:\/\/doi.org\/10.1016\/j.chembiol.2018.09.010 (2018).","journal-title":"Cell Chem. Biol."},{"key":"966_CR59","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1021\/jm901137j","volume":"53","author":"JB Baell","year":"2010","unstructured":"Baell, J. B. & Holloway, G. A. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J. Med Chem. 53, 2719\u20132740, https:\/\/doi.org\/10.1021\/jm901137j (2010).","journal-title":"J. Med Chem."},{"key":"966_CR60","doi-asserted-by":"publisher","unstructured":"Ermakova, S. P. et al. -)-Epigallocatechin gallate overcomes resistance to etoposide-induced cell death by targeting the molecular chaperone glucose-regulated protein 78. Cancer Res. 66, 9260\u20139269, https:\/\/doi.org\/10.1158\/0008-5472.CAN-06-1586(2006).","DOI":"10.1158\/0008-5472.CAN-06-1586"},{"key":"966_CR61","doi-asserted-by":"publisher","first-page":"10214","DOI":"10.1074\/jbc.M512792200","volume":"281","author":"C Li","year":"2006","unstructured":"Li, C. et al. Green tea polyphenols modulate insulin secretion by inhibiting glutamate dehydrogenase. J. Biol. Chem. 281, 10214\u201310221, https:\/\/doi.org\/10.1074\/jbc.M512792200 (2006).","journal-title":"J. Biol. Chem."},{"key":"966_CR62","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.phrs.2015.08.021","volume":"100","author":"MR de Oliveira","year":"2015","unstructured":"de Oliveira, M. R. et al. The effects of baicalein and baicalin on mitochondrial function and dynamics: a review. Pharm. Res. 100, 296\u2013308, https:\/\/doi.org\/10.1016\/j.phrs.2015.08.021 (2015).","journal-title":"Pharm. Res."},{"key":"966_CR63","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/nature09873","volume":"472","author":"S Alavez","year":"2011","unstructured":"Alavez, S., Vantipalli, M. C., Zucker, D. J., Klang, I. M. & Lithgow, G. J. Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature 472, 226\u2013229, https:\/\/doi.org\/10.1038\/nature09873 (2011).","journal-title":"Nature"},{"key":"966_CR64","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3233\/ADR-180087","volume":"3","author":"A Gamir-Morralla","year":"2019","unstructured":"Gamir-Morralla, A., Sacristan, S., Medina, M. & Iglesias, T. Effects of Thioflavin T and GSK-3 inhibition on lifespan and motility in a caenorhabditis elegans model of tauopathy. J. Alzheimers Dis. Rep. 3, 47\u201357, https:\/\/doi.org\/10.3233\/ADR-180087 (2019).","journal-title":"J. Alzheimers Dis. Rep."},{"key":"966_CR65","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/s41586-019-1808-9","volume":"577","author":"BM Burmann","year":"2020","unstructured":"Burmann, B. M. et al. Regulation of alpha-synuclein by chaperones in mammalian cells. Nature 577, 127\u2013132, https:\/\/doi.org\/10.1038\/s41586-019-1808-9 (2020).","journal-title":"Nature"},{"key":"966_CR66","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.tibs.2018.11.005","volume":"44","author":"AD Stephens","year":"2019","unstructured":"Stephens, A. D., Zacharopoulou, M. & Kaminski Schierle, G. S. The cellular environment affects monomeric alpha-Synuclein structure. Trends Biochem. Sci. 44, 453\u2013466, https:\/\/doi.org\/10.1016\/j.tibs.2018.11.005 (2019).","journal-title":"Trends Biochem. Sci."},{"key":"966_CR67","doi-asserted-by":"publisher","first-page":"8468","DOI":"10.1021\/acs.analchem.6b00731","volume":"88","author":"A Konijnenberg","year":"2016","unstructured":"Konijnenberg, A. et al. Opposite structural effects of Epigallocatechin-3-gallate and dopamine binding to alpha-Synuclein. Anal. Chem. 88, 8468\u20138475, https:\/\/doi.org\/10.1021\/acs.analchem.6b00731 (2016).","journal-title":"Anal. Chem."},{"key":"966_CR68","doi-asserted-by":"publisher","first-page":"2740","DOI":"10.1021\/jm030026b","volume":"46","author":"CA Mathis","year":"2003","unstructured":"Mathis, C. A. et al. Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. J. Med. Chem. 46, 2740\u20132754, https:\/\/doi.org\/10.1021\/jm030026b (2003).","journal-title":"J. Med. Chem."},{"key":"966_CR69","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.jsb.2004.08.002","volume":"149","author":"MR Krebs","year":"2005","unstructured":"Krebs, M. R., Bromley, E. H. & Donald, A. M. The binding of thioflavin-T to amyloid fibrils: localisation and implications. J. Struct. Biol. 149, 30\u201337, https:\/\/doi.org\/10.1016\/j.jsb.2004.08.002 (2005).","journal-title":"J. Struct. Biol."},{"key":"966_CR70","doi-asserted-by":"publisher","first-page":"7589","DOI":"10.1039\/d0cc01161d","volume":"56","author":"B Frieg","year":"2020","unstructured":"Frieg, B., Gremer, L., Heise, H., Willbold, D. & Gohlke, H. Binding modes of thioflavin T and Congo red to the fibril structure of amyloid-beta(1-42). Chem. Commun.56, 7589\u20137592, https:\/\/doi.org\/10.1039\/d0cc01161d (2020).","journal-title":"Chem. Commun."},{"key":"966_CR71","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1038\/s41586-022-05319-3","volume":"610","author":"Y Yang","year":"2022","unstructured":"Yang, Y. et al. Structures of alpha-synuclein filaments from human brains with Lewy pathology. Nature 610, 791\u2013795, https:\/\/doi.org\/10.1038\/s41586-022-05319-3 (2022).","journal-title":"Nature"},{"key":"966_CR72","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1038\/s42003-022-03948-y","volume":"5","author":"B Frieg","year":"2022","unstructured":"Frieg, B. et al. Quaternary structure of patient-homogenate amplified alpha-synuclein fibrils modulates seeding of endogenous alpha-synuclein. Commun. Biol. 5, 1040, https:\/\/doi.org\/10.1038\/s42003-022-03948-y (2022).","journal-title":"Commun. Biol."},{"key":"966_CR73","doi-asserted-by":"publisher","unstructured":"Melki, R. Disease mechanisms of multiple system atrophy: what a parallel between the form of pasta and the Alpha-Synuclein Assemblies Involved in MSA and PD Tells Us. Cerebellum. https:\/\/doi.org\/10.1007\/s12311-022-01417-0 (2022).","DOI":"10.1007\/s12311-022-01417-0"},{"key":"966_CR74","doi-asserted-by":"publisher","unstructured":"De Giorgi, F. et al. Novel self-replicating alpha-synuclein polymorphs that escape ThT monitoring can spontaneously emerge and acutely spread in neurons. Sci. Adv. 6. https:\/\/doi.org\/10.1126\/sciadv.abc4364 (2020).","DOI":"10.1126\/sciadv.abc4364"},{"key":"966_CR75","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.jmb.2009.09.056","volume":"394","author":"C Wu","year":"2009","unstructured":"Wu, C., Biancalana, M., Koide, S. & Shea, J. E. Binding modes of thioflavin-T to the single-layer beta-sheet of the peptide self-assembly mimics. J. Mol. Biol. 394, 627\u2013633, https:\/\/doi.org\/10.1016\/j.jmb.2009.09.056 (2009).","journal-title":"J. Mol. Biol."},{"key":"966_CR76","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/s41594-020-0384-x","volume":"27","author":"CPA Doherty","year":"2020","unstructured":"Doherty, C. P. A. et al. A short motif in the N-terminal region of alpha-synuclein is critical for both aggregation and function. Nat. Struct. Mol. Biol. 27, 249\u2013259, https:\/\/doi.org\/10.1038\/s41594-020-0384-x (2020).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"966_CR77","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.bbadis.2005.11.009","volume":"1762","author":"G Griffioen","year":"2006","unstructured":"Griffioen, G. et al. A yeast-based model of alpha-synucleinopathy identifies compounds with therapeutic potential. Biochim. Biophys. Acta 1762, 312\u2013318, https:\/\/doi.org\/10.1016\/j.bbadis.2005.11.009 (2006).","journal-title":"Biochim. Biophys. Acta"},{"key":"966_CR78","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1007\/s11064-009-0038-1","volume":"35","author":"L Ma","year":"2010","unstructured":"Ma, L. et al. Genome-wide microarray analysis of the differential neuroprotective effects of antioxidants in neuroblastoma cells overexpressing the familial Parkinson\u2019s disease alpha-synuclein A53T mutation. Neurochem Res. 35, 130\u2013142, https:\/\/doi.org\/10.1007\/s11064-009-0038-1 (2010).","journal-title":"Neurochem Res."},{"key":"966_CR79","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1111\/j.1471-4159.2010.06752.x","volume":"114","author":"M Jiang","year":"2010","unstructured":"Jiang, M. et al. Baicalein reduces E46K alpha-synuclein aggregation in vitro and protects cells against E46K alpha-synuclein toxicity in cell models of familiar Parkinsonism. J. Neurochem. 114, 419\u2013429, https:\/\/doi.org\/10.1111\/j.1471-4159.2010.06752.x (2010).","journal-title":"J. Neurochem."},{"key":"966_CR80","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1007\/s12640-019-00015-z","volume":"35","author":"FV Santa-Cecilia","year":"2019","unstructured":"Santa-Cecilia, F. V., Leite, C. A., Del-Bel, E. & Raisman-Vozari, R. The neuroprotective effect of doxycycline on neurodegenerative diseases. Neurotox. Res. 35, 981\u2013986, https:\/\/doi.org\/10.1007\/s12640-019-00015-z (2019).","journal-title":"Neurotox. Res."},{"key":"966_CR81","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1016\/j.bbadis.2016.07.008","volume":"1862","author":"Q Hu","year":"2016","unstructured":"Hu, Q. et al. Baicalein inhibits alpha-synuclein oligomer formation and prevents progression of alpha-synuclein accumulation in a rotenone mouse model of Parkinson\u2019s disease. Biochim. Biophys. Acta 1862, 1883\u20131890, https:\/\/doi.org\/10.1016\/j.bbadis.2016.07.008 (2016).","journal-title":"Biochim. Biophys. Acta"},{"key":"966_CR82","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.neuroscience.2014.12.003","volume":"286","author":"M Chen","year":"2015","unstructured":"Chen, M. et al. Tea polyphenols alleviate motor impairments, dopaminergic neuronal injury, and cerebral alpha-synuclein aggregation in MPTP-intoxicated parkinsonian monkeys. Neuroscience 286, 383\u2013392, https:\/\/doi.org\/10.1016\/j.neuroscience.2014.12.003 (2015).","journal-title":"Neuroscience"},{"key":"966_CR83","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67133-z","volume":"10","author":"CR Goodlett","year":"2020","unstructured":"Goodlett, C. R. et al. Evaluation of the therapeutic potential of Epigallocatechin-3-gallate (EGCG) via oral gavage in young adult Down syndrome mice. Sci. Rep. 10, 10426. https:\/\/doi.org\/10.1038\/s41598-020-67133-z (2020).","journal-title":"Sci. Rep."},{"key":"966_CR84","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1046\/j.1460-9568.2000.00076.x","volume":"12","author":"H Hirling","year":"2000","unstructured":"Hirling, H. et al. Syntaxin 13 is a developmentally regulated SNARE involved in neurite outgrowth and endosomal trafficking. Eur. J. Neurosci. 12, 1913\u20131923, https:\/\/doi.org\/10.1046\/j.1460-9568.2000.00076.x (2000).","journal-title":"Eur. J. Neurosci."},{"key":"966_CR85","doi-asserted-by":"publisher","first-page":"1900","DOI":"10.1111\/j.1471-4159.1988.tb02495.x","volume":"50","author":"S Schinelli","year":"1988","unstructured":"Schinelli, S., Zuddas, A., Kopin, I. J., Barker, J. L. & di Porzio, U. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine metabolism and 1-methyl-4-phenylpyridinium uptake in dissociated cell cultures from the embryonic mesencephalon. J. Neurochem 50, 1900\u20131907, https:\/\/doi.org\/10.1111\/j.1471-4159.1988.tb02495.x (1988).","journal-title":"J. Neurochem"},{"key":"966_CR86","doi-asserted-by":"publisher","DOI":"10.1093\/bioadv\/vbab041","volume":"2","author":"JP Quast","year":"2022","unstructured":"Quast, J. P., Schuster, D. & Picotti, P. protti: an R package for comprehensive data analysis of peptide- and protein-centric bottom-up proteomics data. Bioinform. Adv. 2, vbab041. https:\/\/doi.org\/10.1093\/bioadv\/vbab041 (2022).","journal-title":"Bioinform. Adv."}],"container-title":["npj Parkinson's Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41531-025-00966-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-025-00966-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-025-00966-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T12:37:13Z","timestamp":1746880633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41531-025-00966-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,10]]},"references-count":86,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["966"],"URL":"https:\/\/doi.org\/10.1038\/s41531-025-00966-5","relation":{},"ISSN":["2373-8057"],"issn-type":[{"value":"2373-8057","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,10]]},"assertion":[{"value":"6 November 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"AC Immune (ACI) provided two of the compounds used in the study and Ait-Bouziad, N., Davranche, A., Boudou, C., Tsika, E., Ouared, A., and St\u00f6hr, J. are employees of ACI. LiP-MS is subject of a patent licensed to the company Biognosys. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"122"}}