000110683 001__ 110683
000110683 005__ 20230519145559.0
000110683 0247_ $$2doi$$a10.1038/s41467-021-24039-2
000110683 0248_ $$2sideral$$a126796
000110683 037__ $$aART-2021-126796
000110683 041__ $$aeng
000110683 100__ $$aSantos, J.
000110683 245__ $$aa-Helical peptidic scaffolds to target a-synuclein toxic species with nanomolar affinity
000110683 260__ $$c2021
000110683 5060_ $$aAccess copy available to the general public$$fUnrestricted
000110683 5203_ $$aa-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).
000110683 536__ $$9info:eu-repo/grantAgreement/ES/MCIU-FEDER/PGC2018-096335-B-100$$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/BFU2015-64119-P$$9info:eu-repo/grantAgreement/ES/MINECO/RYC-2012-12068
000110683 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000110683 590__ $$a17.694$$b2021
000110683 592__ $$a4.846$$b2021
000110683 594__ $$a23.2$$b2021
000110683 591__ $$aMULTIDISCIPLINARY SCIENCES$$b6 / 74 = 0.081$$c2021$$dQ1$$eT1
000110683 593__ $$aChemistry (miscellaneous)$$c2021$$dQ1
000110683 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2021$$dQ1
000110683 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000110683 700__ $$aGracia, P.$$uUniversidad de Zaragoza
000110683 700__ $$aNavarro, S.
000110683 700__ $$aPeña-Díaz, S.
000110683 700__ $$aPujols, J.
000110683 700__ $$0(orcid)0000-0002-9138-6687$$aCremades, N.$$uUniversidad de Zaragoza
000110683 700__ $$aPallarès, I.
000110683 700__ $$aVentura, S.
000110683 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000110683 773__ $$g12, 1 (2021), 3752 [14 pp]$$tNature communications$$x2041-1723
000110683 8564_ $$s4629834$$uhttps://zaguan.unizar.es/record/110683/files/texto_completo.pdf$$yVersión publicada
000110683 8564_ $$s1308846$$uhttps://zaguan.unizar.es/record/110683/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000110683 909CO $$ooai:zaguan.unizar.es:110683$$particulos$$pdriver
000110683 951__ $$a2023-05-18-15:58:54
000110683 980__ $$aARTICLE