Peptidomimetics Inspired by α-Synuclein or Its Chaperone αB-Crystallin Differentially Modulate α-Synuclein Aggregation.
Peptidomimetics Inspired by α-Synuclein or Its Chaperone αB-Crystallin Differentially Modulate α-Synuclein Aggregation.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Orsay, FR · Author affiliation
Université Paris-Saclay, CNRS, BioCIS, Bat. Henri Moissan, 17 av. des Sciences, 91400 Orsay, France.Location evidence
Milan, IT · Author affiliation
Department of Biosciences, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.Location evidence
Strasbourg, FR · Author affiliation
Laboratory of Chemoinformatics, Faculty of Chemistry, Université de Strasbourg, 67081 Strasbourg, France.Location evidence
Düsseldorf, DE · Author affiliation
Institut für Physikalische Biologie, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, 40204 Düsseldorf, Germany.Location evidence
Segrate, IT · Author affiliation
Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Via Fratelli Cervi 93, Segrate, 20054 Milano, Italy.Location evidence
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Original abstract
Aggregation of the α-Synuclein (αSyn) protein in neurons is responsible for synucleinopathies such as Parkinson's disease. In healthy cells, αSyn is primarily present as monomers. Under pathological conditions, oligomers and fibrils are formed, leading to neuronal toxicity and death. No treatment prevents fatal synucleinopathies. We designed small peptidomimetics based on the structure of αSyn aggregates and on its chaperone protein αB-Crystallin. Interestingly, a relationship between the impact of peptidomimetics on the αSyn aggregation process, their sequences, and secondary conformation has been evidenced. In vitro and in cellular assays demonstrated that one compound based on αB-Crystallin was able to interfere with αSyn folding and aggregation by reducing the formation of oligomers and promoting off-pathway aggregation. The demonstration that physiological chaperone proteins can be mimicked by small peptide derivatives paves the way for new strategies to design inhibitors of amyloid protein aggregation, a hallmark of around 50 neurodegenerative and systemic amyloid diseases.