Intracellular spatially-targeted chemical chaperones increase native state stability of mutant SOD1 barrel.
| Autor: | Ribeiro SS; Institute of Physical and Theoretical Chemistry, TU Braunschweig, D-38106 Braunschweig, Germany.; Braunschweig Integrated Centre of Systems Biology (BRICS), D-38106 Braunschweig, Germany., Gnutt D; Institute of Physical and Theoretical Chemistry, TU Braunschweig, D-38106 Braunschweig, Germany.; Braunschweig Integrated Centre of Systems Biology (BRICS), D-38106 Braunschweig, Germany.; Institute of Physical Chemistry II, Ruhr University, D-44780 Bochum, Germany., Azoulay-Ginsburg S; Department of Chemistry, Bar-Ilan University, Ramat-Gan 5290002, Israel., Fetahaj Z; Institute of Physical Chemistry II, Ruhr University, D-44780 Bochum, Germany., Spurlock E; Institute of Physical and Theoretical Chemistry, TU Braunschweig, D-38106 Braunschweig, Germany.; Braunschweig Integrated Centre of Systems Biology (BRICS), D-38106 Braunschweig, Germany., Lindner F; Institute of Physical and Theoretical Chemistry, TU Braunschweig, D-38106 Braunschweig, Germany.; Braunschweig Integrated Centre of Systems Biology (BRICS), D-38106 Braunschweig, Germany., Kuz D; Institute of Physical and Theoretical Chemistry, TU Braunschweig, D-38106 Braunschweig, Germany.; Braunschweig Integrated Centre of Systems Biology (BRICS), D-38106 Braunschweig, Germany., Cohen-Erez Y; Department of Biotechnology Engineering, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, P.O. Box 653, Beer Sheva 84105, Israel., Rapaport H; Department of Biotechnology Engineering, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, P.O. Box 653, Beer Sheva 84105, Israel., Israelson A; Department of Physiology and Cell Biology, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, P.O. Box 653, Beer Sheva 84105, Israel., Gruzman AL; Department of Chemistry, Bar-Ilan University, Ramat-Gan 5290002, Israel., Ebbinghaus S; Institute of Physical and Theoretical Chemistry, TU Braunschweig, D-38106 Braunschweig, Germany.; Braunschweig Integrated Centre of Systems Biology (BRICS), D-38106 Braunschweig, Germany.; Institute of Physical Chemistry II, Ruhr University, D-44780 Bochum, Germany.; Research Center Chemical Sciences and Sustainability, Research Alliance Ruhr, Duisburg, Germany. |
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| Jazyk: | angličtina |
| Zdroj: | Biological chemistry [Biol Chem] 2023 Aug 09; Vol. 404 (10), pp. 909-930. Date of Electronic Publication: 2023 Aug 09 (Print Publication: 2023). |
| DOI: | 10.1515/hsz-2023-0198 |
| Abstrakt: | Amyotrophic lateral sclerosis (ALS) is a progressive neurological disorder with currently no cure. Central to the cellular dysfunction associated with this fatal proteinopathy is the accumulation of unfolded/misfolded superoxide dismutase 1 (SOD1) in various subcellular locations. The molecular mechanism driving the formation of SOD1 aggregates is not fully understood but numerous studies suggest that aberrant aggregation escalates with folding instability of mutant apoSOD1. Recent advances on combining organelle-targeting therapies with the anti-aggregation capacity of chemical chaperones have successfully reduce the subcellular load of misfolded/aggregated SOD1 as well as their downstream anomalous cellular processes at low concentrations (micromolar range). Nevertheless, if such local aggregate reduction directly correlates with increased folding stability remains to be explored. To fill this gap, we synthesized and tested here the effect of 9 ER-, mitochondria- and lysosome-targeted chemical chaperones on the folding stability of truncated monomeric SOD1 (SOD1 (© 2023 the author(s), published by De Gruyter, Berlin/Boston.) |
| Databáze: | MEDLINE |
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