Cathepsin B-Induced Degradation of Lysozyme Amyloid Fibrils

first_page Download PDF settings Order Article Reprints Font Type: Arial Georgia Verdana Font Size: Aa Aa Aa Line Spacing:    Column Width:    Background: Open AccessAbstract Cathepsin B-Induced Degradation of Lysozyme Amyloid Fibrils † by Maksim I. SulatskyMaksim I. Sulatsky SciProfiles Scilit Preprints.org Google Scholar 1, Olga V. StepanenkoOlga V. Stepanenko SciProfiles Scilit Preprints.org Google Scholar 2, Olesya V. StepanenkoOlesya V. Stepanenko SciProfiles Scilit Preprints.org Google Scholar 2, Ekaterina V. MikhailovaEkaterina V. Mikhailova SciProfiles Scilit Preprints.org Google Scholar 2 and Anna I. SulatskayaAnna I. Sulatskaya SciProfiles Scilit Preprints.org Google Scholar 2,* 1 Laboratory of Cell Morphology, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., 194064 St. Petersburg, Russia 2 Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., 194064 St. Petersburg, Russia * Author to whom correspondence should be addressed. † Presented at the 3rd International Electronic Conference on Biomolecules, 23–25 April 2024; Available online: https://sciforum.net/event/IECBM2024. Proceedings 2024, 103(1), 18; https://doi.org/10.3390/proceedings2024103018 Published: 12 April 2024 Download keyboard_arrow_down Download PDF Download PDF with Cover Download XML Download Epub Versions Notes Keywords: amyloidosis treatment; amyloid fibrils; amyloid-destructed factors; cathepsin B; mechanisms and products of amyloid degradation; cytotoxicity Diseases associated with the accumulation of ordered protein aggregates, amyloid fibrils, once thought to be rare, are predicted to soon become epidemics. However, there are still no effective drugs without serious side effects for the degradation of amyloid plaques, which is currently considered a promising therapeutic strategy. We tested the proteolytic enzyme cathepsin B, involved in the cellular immune response, as a potential amyloid-degrading agent.Our investigation focused on model lysozyme amyloid fibrils that accumulate in systemic non-neuropathic hereditary amyloidosis. Various microscopic, biochemical, and spectroscopic approaches were used to study the properties of amyloids and their degradation products. We showed that cathepsin B-mediated proteolysis of amyloid-forming proteins led to fibril fragmentation. In some amyloid fragments, the loss of an ordered structure was also observed. The identified effects can be attributed to the disruption of intra- and intermolecular hydrogen bonds in the fibril core. At the same time, with the stepwise addition of cathepsin B (as opposed to a one-step enzyme addition at the same concentration), we observed a lower number of "fluffed" fragments, although the efficiency of amyloid degradation remained practically unchanged. Cathepsin B deactivation did not lead to fibril reassembly (as is the case with other amyloid-degrading factors) for at least 5 days. Despite the observed cathepsin B-induced degradation of amyloids, cell viability was not increased in its presence, indicating an equally high cytotoxicity of intact amyloids and of their degradation products.The results of our study show that the visible destruction of amyloid fibrils does not always lead to a decrease in their cytotoxicity. However, the transformation of amyloids into smaller and less stable aggregates with an altered structure (as effected by cathepsin B) is an important step in the development of effective and safe anti-amyloid agents. Author ContributionsConceptualization, A.I.S.; formal analysis, M.I.S., O.V.S. (Olga V. Stepanenko), O.V.S. (Olesya V. Stepanenko), E.V.M., A.I.S.; investigation, M.I.S., O.V.S. (Olga V. Stepanenko), O.V.S. (Olesya V. Stepanenko), E.V.M., A.I.S.; writing—original draft preparation, M.I.S.; writing—review and editing, M.I.S., O.V.S. (Olga V. Stepanenko), O.V.S. (Olesya V. Stepanenko), E.V.M., A.I.S.; supervision, A.I.S.; funding acquisition, A.I.S. All authors have read and agreed to the published version of the manuscript.FundingThis research was funded by the Russian Science Foundation (grant No. 23-74-10092).Institutional Review Board StatementNot applicable.Informed Consent StatementNot applicable.Data Availability StatementThe data that support the findings of this study are available from the corresponding author upon reasonable request.Conflicts of InterestThe authors declare no conflict of interest.Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Share and Cite MDPI and ACS Style Sulatsky, M.I.; Stepanenko, O.V.; Stepanenko, O.V.; Mikhailova, E.V.; Sulatskaya, A.I. Cathepsin B-Induced Degradation of Lysozyme Amyloid Fibrils. Proceedings 2024, 103, 18. https://doi.org/10.3390/proceedings2024103018 AMA Style Sulatsky MI, Stepanenko OV, Stepanenko OV, Mikhailova EV, Sulatskaya AI. Cathepsin B-Induced Degradation of Lysozyme Amyloid Fibrils. Proceedings. 2024; 103(1):18. https://doi.org/10.3390/proceedings2024103018 Chicago/Turabian Style Sulatsky, Maksim I., Olga V. Stepanenko, Olesya V. Stepanenko, Ekaterina V. Mikhailova, and Anna I. Sulatskaya. 2024. 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