期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-24039-2
关键词
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资金
- Spanish Ministry of Economy and Competitiveness (MINECO) [BIO2016-78310-R, BIO2017-91475-EXP]
- Ministry of Science and Innovation (MICINN) [PID2019-105017RB-I00]
- ICREA, ICREA-Academia 2015
- MINECO [RYC-2012-12068]
- MINECO/FEDER
- EU [BFU2015-64119-P, PGC2018-096335-B-100]
- MICIU/FEDER
- MICINN [FPU17/01157]
Researchers have identified a class of peptides that can bind toxic α-synuclein oligomers and amyloid fibrils without interfering with monomeric functional protein, preventing further aggregation and associated cell damage.
alpha -Synuclein aggregation is a key driver of neurodegeneration in Parkinson's disease and related syndromes. Accordingly, obtaining a molecule that targets alpha -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 alpha -helical peptides that bind to these alpha -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 alpha -synuclein species. alpha -Synuclein (alpha S) aggregation is a driver of several neurodegenerative disorders. Here, the authors identify a class of peptides that bind toxic alpha S oligomers and amyloid fibrils but not monomeric functional protein, and prevent further alpha S aggregation and associated cell damage.
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