Details

Autor(en) / Beteiligte

• Pujols, Jordi
• Peña-Díaz, Samuel
• Conde-Giménez, María
• Pinheiro, Francisca
• Navarro, Susanna
• Sancho, Javier
• Ventura, Salvador

Titel

High-Throughput Screening Methodology to Identify Alpha-Synuclein Aggregation Inhibitors

Ist Teil von

• International journal of molecular sciences, 2017-03, Vol.18 (3), p.478-478

Ort / Verlag

Switzerland: MDPI

Erscheinungsjahr

2017

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• An increasing number of neurodegenerative diseases are being found to be associated with the abnormal accumulation of aggregated proteins in the brain. In Parkinson's disease, this process involves the aggregation of alpha-synuclein (α-syn) into intraneuronal inclusions. Thus, compounds that inhibit α-syn aggregation represent a promising therapeutic strategy as disease-modifying agents for neurodegeneration. The formation of α-syn amyloid aggregates can be reproduced in vitro by incubation of the recombinant protein. However, the in vitro aggregation of α-syn is exceedingly slow and highly irreproducible, therefore precluding fast high throughput anti-aggregation drug screening. Here, we present a simple and easy-to-implement in-plate method for screening large chemical libraries in the search for α-syn aggregation modulators. It allows us to monitor aggregation kinetics with high reproducibility, while being faster and requiring lower protein amounts than conventional aggregation assays. We illustrate how the approach enables the identification of strong aggregation inhibitors in a library of more than 14,000 compounds.