110683 20230519145559.0 doi 10.1038/s41467-021-24039-2 sideral 126796 ART-2021-126796 eng Santos, J. a-Helical peptidic scaffolds to target a-synuclein toxic species with nanomolar affinity 2021 Access copy available to the general public Unrestricted a-Synuclein aggregation is a key driver of neurodegeneration in Parkinson’s disease and related syndromes. Accordingly, obtaining a molecule that targets a-synuclein toxic assemblies with high affinity is a long-pursued objective. Here, we exploit the biophysical properties of toxic oligomers and amyloid fibrils to identify a family of a-helical peptides that bind to these a-synuclein species with low nanomolar affinity, without interfering with the monomeric functional protein. This activity is translated into a high anti-aggregation potency and the ability to abrogate oligomer-induced cell damage. Using a structure-guided search we identify a human peptide expressed in the brain and the gastrointestinal tract with analogous binding, anti-aggregation, and detoxifying properties. The chemical entities we describe here may represent a therapeutic avenue for the synucleinopathies and are promising tools to assist diagnosis by discriminating between native and toxic a-synuclein species. © 2021, The Author(s). info:eu-repo/grantAgreement/ES/MCIU-FEDER/PGC2018-096335-B-100 info:eu-repo/grantAgreement/ES/MINECO-FEDER/BFU2015-64119-P info:eu-repo/grantAgreement/ES/MINECO/RYC-2012-12068 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 17.694 2021 MULTIDISCIPLINARY SCIENCES 6 / 74 = 0.081 2021 Q1 T1 4.846 2021 Chemistry (miscellaneous) 2021 Q1 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2021 Q1 23.2 2021 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Gracia, P. Universidad de Zaragoza Navarro, S. Peña-Díaz, S. Pujols, J. Cremades, N. Universidad de Zaragoza (orcid)0000-0002-9138-6687 Pallarès, I. Ventura, S. 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 12, 1 (2021), 3752 [14 pp] Nature communications 2041-1723 4629834 http://zaguan.unizar.es/record/110683/files/texto_completo.pdf Versión publicada 1308846 http://zaguan.unizar.es/record/110683/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:110683 articulos driver 2023-05-18-15:58:54 ARTICLE