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Pàgina inicial > Articles > Articles publicats > α-Helical peptidic scaffolds to target α-synuclein toxic species with nanomolar affinity |
Data: | 2021 |
Resum: | α-Synuclein aggregation is a key driver of neurodegeneration in Parkinson's disease and related syndromes. Accordingly, obtaining a molecule that targets α-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 α-helical peptides that bind to these α-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 α-synuclein species. α-Synuclein (αS) aggregation is a driver of several neurodegenerative disorders. Here, the authors identify a class of peptides that bind toxic αS oligomers and amyloid fibrils but not monomeric functional protein, and prevent further αS aggregation and associated cell damage. |
Ajuts: | Ministerio de Economía y Competitividad BIO2016-78310-R Ministerio de Economía y Competitividad BIO2017-91475-EXP Agencia Estatal de Investigación PID2019-105017RB-I00 Ministerio de Economía y Competitividad RYC-2012-12068 Ministerio de Economía y Competitividad BFU2015-64119-P Agencia Estatal de Investigación PGC2018-096335-B-I00 Ministerio de Ciencia e Innovación FPU17/01157 |
Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | Peptides ; Biophysics ; Protein aggregation ; Protein design |
Publicat a: | Nature communications, Vol. 12 (June 2021) , art. 3752, ISSN 2041-1723 |
14 p, 4.4 MB |