α-Helical peptidic scaffolds to target α-synuclein toxic species with nanomolar affinity

JAIME SANTOS SUAREZ, Pablo Gracia, Susanna Navarro, Samuel Peña-Díaz, Jordi Pujols, Nunilo Cremades, Irantzu Pallarès, Salvador Ventura

Producción científica: Contribución a una revistaArtículoInvestigaciónrevisión exhaustiva

46 Citas (Web of Science)

Resumen

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.

Idioma originalInglés
Número de artículo3752
Páginas (desde-hasta)3752
Número de páginas14
PublicaciónNature communications
Volumen12
N.º1
DOI
EstadoPublicada - 1 dic 2021

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